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ABSTRACT Multiple myeloma (MM) is an incurable blood malignancy characterized by the clonal expansion of plasma cells and the secretion of monoclonal immunoglobulins. High‐risk MM, defined by specific cytogenetic abnormalities, poses significant therapeutic challenges and is associated with inferior survival outcomes compared to standard‐risk disease. Although molecularly targeted therapies have shown efficacy in other hematologic malignancies, currently venetoclax is the only targeted therapy approved for MM (t(11;14)). However, chromosome 1q gains, amplifications, and 1p deletions are frequently observed in MM, and have been linked to drug resistance and poor patient prognosis. Accordingly, this review focuses on emerging MM precision therapies capable of targeting dysregulated genes within these regions. It addresses gene therapies, small molecule inhibitors and monoclonal antibodies currently under investigation to antagonize oncogenic drivers including MCL‐1, BCL9, F11R, and CKS1B, all of which are implicated in cell survival, proliferation or drug resistance. In conclusion, the link between chromosome 1 abnormalities and high‐risk disease in MM patients offers a compelling rationale to identify and explore therapeutic targeting of chromosome 1 gene products as a novel precision medicine approach for a poorly served patient population. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia raises the risk for cardiovascular complications and overall health. Hypercholesterolemia is common, affecting 10% of the general population of the US, and heritable. Most individuals with hypercholesterolemia have a polygenic predisposition to the condition. Previously we identified a quantitative trait locus, Tachol1, linked to hypercholesterolemia on mouse chromosome 1 (Chr1) in a cross between C57BL/6J (B6) and TALLYHO/JngJ (TH) mice, a polygenic model for human obesity, type 2 diabetes and hyperlipidemia. Subsequently, using congenic mice that carry a TH-derived genomic segment of Chr1 on a B6 background, we demonstrated that the distal segment of Chr1, where Tachol1 maps, is necessary to cause hypercholesterolemia, as well as diet-induced obesity. In this study, we generated overlapping subcongenic lines to the distal segment of congenic region and characterized subcongenic mice carrying the smallest TH region of Tachol1, ~ 16.2 Mb in size (B6.TH-Chr1-16.2 Mb). Both male and female B6.TH-Chr1-16.2 Mb mice showed a significantly increased plasma total cholesterol levels compared to B6 on both chow and high fat (HF) diet. B6.TH-Chr1-16.2 Mb mice also had greater fat mass than B6 on HF diet, without increasing food intake. The gene and protein expression levels of absent in melanoma 2 (Aim2) gene were significantly upregulated in B6.TH-Chr1-16.2 Mb mice compared to B6. In summary, we confirmed the effect of Tachol1 on hypercholesterolemia and diet-induced obesity using subcongenic analysis. [ABSTRACT FROM AUTHOR]

Background: Chromosome-1 abnormalities (C1As) are common genetic aberrations in hematological malignancies. We sought to evaluate significance of these abnormalities with reference to clinical characteristics and survival outcome in a pediatric B-Lymphoblastic Leukemia (B-ALL) cohort. Methods: This is a retrospective study conducted in cytogenetic section of Indus Hospital and Health Network. Data was retrieved from October 2020 to July 2022 for childhood B-ALL cases exhibiting C1As. Chromosome analysis was performed on Cytovision MB8 using G-banded metaphases derived from unstimulated bone marrow culture. Results were recorded according to the International System for Human Cytogenetic Nomenclature (ISCN-2020). Data analyzed using SPSS, version 24.0. Results: C1As were observed in 60/450 (13.3%) cases of B-ALL. Among C1As, 29 (48%) cases had t(1;19). There were 13 (45%) balanced and 16 (55%) unbalanced translocations. The aberrations without t(1;19) were seen in 31 (52%) cases including 1q duplication with hyperdiploidy in 14 (45%) cases. The median age for C1As with and without t(1;19) was eight years and six years while the median leukocyte count was 32 x 109/L vs. 17 x 109/L. Event-free survival (EFS) for cases with and without t(1;19) was 69% and 74.2% respectively. Conclusion: Despite the fact that the t(1;19) positive group had a higher median age, a higher white cell count and more CNS positives, the difference in EFS is statistically insignificant when compared to the t(1;19) negative cases. Furthermore, we found a survival difference between balanced and unbalanced t(1;19) groups, which is statistically insignificant but warrants large-scale prospective studies for further understanding. [ABSTRACT FROM AUTHOR]

Abstract Background Gout is a highly hereditary disease, but not all those carrying well-known risk variants have developing gout attack even in hyperuricemia status. We performed a genome-wide association study (GWAS) and polygenic risk score (PRS) analysis to illustrate the new genetic architectures of gout and asymptomatic hyperuricemia (AH). Methods GWAS was performed to identify variants associated with gout/AH compared with normouricemia. The participants were males, enrolled from the Taiwan Biobank and China Medical University, and divided into discovery (n=39,594) and replication (n=891) cohorts for GWAS. For PRS analysis, the discovery cohort was grouped as base (n=21,814) and target (n=17,780) cohorts, and the score was estimated by grouping the polymorphisms into protective or not for the phenotypes in the base cohort. Results The genes ABCG2 and SLC2A9 were found as the major genetic factors governing gouty and AH, and even in those carrying the rs2231142 (ABCG2) wild-genotype. Surprisingly, variants on chromosome 1, such as rs7546668 (DNAJC16), rs10927807 (AGMAT), rs9286836 (NUDT17), rs4971100 (TRIM46), rs4072037 (MUC1), and rs2974935 (MTX1), showed significant associations with gout in both discovery and replication cohorts (all p-values < 1e−8). Concerning the PRS, the rates of gout and AH increased with increased quartile PRS in those SNPs having risk effects on the phenotypes; on the contrary, gout/AH rates decreased with increased quartile PRS in those protective SNPs. Conclusions We found new variants on chromosome 1 significantly relating to gout, and PRS predicts the risk of developing gout/AH more robustly based on the SNPs’ effect types on the trait.

Abstract Background Deletion of 1p is associated with poor prognosis in neuroblastoma, however selected 1p-intact patients still experience poor outcomes. Since mutations of 1p genes may mimic the deleterious effects of chromosomal loss, we studied the incidence, spectrum and effects of mutational variants in 1p-intact neuroblastoma. Methods We characterized the 1p status of 325 neuroblastoma patients, and correlated the mutational status of 1p tumor suppressors and neuroblastoma candidate genes with survival outcomes among 100 1p-intact cases, then performed functional validation of selected novel variants of 1p36 genes identified from our patient cohort. Results Among patients with adverse disease characteristics, those who additionally had 1p deletion had significantly worse overall survival. Among 100 tumor-normal pairs sequenced, somatic mutations of 1p tumor suppressors KIF1Bβ and CHD5 were most frequent (2%) after ALK and ATRX (8%), and BARD1 (3%). Mutations of neuroblastoma candidate genes were associated with other synchronous mutations and concurrent 11q deletion (P = 0.045). In total, 24 of 38 variants identified were novel and predicted to be deleterious or pathogenic. Functional validation identified novel KIF1Bβ I1355M variant as a gain-of-function mutation with increased expression and tumor suppressive activity, correlating with indolent clinical behavior; another novel variant CHD5 E43Q was a loss-of-function mutation with decreased expression and increased long-term cell viability, corresponding with aggressive disease characteristics. Conclusions Our study showed that chromosome 1 gene mutations occurred frequently in 1p-intact neuroblastoma, but may not consistently abrogate the function of bonafide 1p tumor suppressors. These findings may augment the evolving model of compounding contributions of 1p gene aberrations toward tumor suppressor inactivation in neuroblastoma.

Abstract Background Rearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynostosis, dysmorphic face, ocular defects, cleft palate, urinary tract anomalies and hand/foot abnormalities. Case presentation Hereby, we report on an Italian female newborn with craniosynostosis, facial dysmorphisms including bilateral microphthalmia and coloboma, cleft palate, and a severe global developmental and growth delay, associated to a 1p31.3p22.2 deletion of 20.7 Mb. This was inherited from the healthy mother, who was carrier of a smaller (2.6 Mb) deletion included within the centromeric region (1p22.3p22.2) of the same rearrangement, in addition to a translocation between chromosomes 1p and 4q. The deleted region of the proband contains about ninety genes. We focus on the genotype–phenotype correlations. Conclusions The results of the present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome. It is hard to establish whether the critical rearrangement of such syndrome may involve the centromeric band p22.3p22.2, or more likely do not, also in light of the genomic profile of the healthy mother of our patient. Neonatologists and pediatricians should take into consideration 1p31 microdeletion in cases of developmental and growth delay associated to craniosynostosis, peculiar facial dysmorphisms, cleft palate and hand/foot abnormalities. The present report provides new data about 1p31 microdeletion syndrome, in view of a better characterization of its genomic and phenotypic profile.

Focal facial dermal dysplasias type III (FFDD III), commonly known as Setleis syndrome (SS; Online Mendelian Inheritance in Man #227260), is a type of focal facial dermal dysplasia, characterized by bitemporal atrophic skin lesion. The homozygous mutations in the TWIST2 gene and copy number variants (CNV) at chromosome 1p36.22p36.21 were reported as the pathogenic mechanism. In this study, we collected DNA samples from a large Chinese family affected by FFDD and found no mutation of TWSIT2. To determine the underlying genetic cause, we performed a multipoint parameter linkage analysis and haplotype analysis of the family 1 and mapped SS to a region Chr1:14.074–20.524cM (rs2401090–rs2294642). Copy number variant was identified by Sanger sequencing, which breakpoints were Chr1:11695972 and Chr1:11829858. The region contains eight genes, including FBXO2, FBXO44, FBXO6, MAD2L2, DRAXIN, AK125437, AGTRAP, and C1orf167. There were no candidate gene mutations of the second family with SS. Our study further reduced the size of CNV resulting in SS (Chr1:11696993–11829858) and focused on eight genes. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial carcinomas (ECs), the most frequent type of uterine body cancer, are highly heterogeneous with overlapping clinical, pathological, and molecular features. This study aimed to gain insights into these cancers' chromosomal and genomic aberration patterns as well as their gene and miRNA expression profiles, all of which are both pathogenetically and clinically important disease features. We found that chromosome 1 was the most frequently rearranged chromosome, mostly leading to gain of 1q, that the genes PTEN, PDGFRA, PIK3CA, and KIT were the most frequent pathogenic variants, and that some other genes and miRNAs of known importance in carcinogenesis and the immune response showed consistent deregulation. This study confirms that a high degree of genetic heterogeneity characterizes EC tumors but highlights the nonrandom involvement of some loci. Endometrial carcinomas (ECs) are histologically classified as endometrioid and nonendometrioid tumors, with each subgroup displaying different molecular profiles and clinical outcomes. Considerable biological and clinical heterogeneity exists within this scheme, however, reflecting its imperfection. We aimed to gather additional data that might help clarify the tumors' pathogenesis and contribute toward a more meaningful classification scheme. In total, 33 ECs were examined for the presence of chromosomal aberrations, genomic imbalances, pathogenic variants, microsatellite instability, and expression profiles at both gene and miRNA levels. Chromosome 1 was the most frequently rearranged chromosome, showing a gain of all or part of the long arm. Pathogenic variants were found for PTEN (53%), PDGFRA (37%), PIK3CA (34%), and KIT (31%). High microsatellite instability was identified in 15 ECs. Comparing tumors and controls, we identified 23 differentially expressed genes of known importance in carcinogenesis, 15 genes involved in innate and adaptative immune responses, and altered expression of 7 miRNAs. miR-32-5p was the most upregulated. Our series showed a high degree of heterogeneity. Tumors were well-separated from controls, but there was no clear-cut separation between endometrioid and nonendometrioid ECs. Whether this means that the current phenotypic classification is of little relevance or if one still has not detected which genomic parameters to enter into correlation analyses remains unknown. [ABSTRACT FROM AUTHOR]

These patients share several features with our patient, including DD (5 patients), scoliosis (4 patients), strabismus, and hypotonia (2 patients). [19] In patient 14 the deletion was more distal and corresponded only partially to the interval described in the 1q21.1 microdeletion syndrome, consequently, it was not clear if the deletion could explain the phenotype and was classified as LP. Keywords: chromosome 1; copy number variant; array comparative genomic hybridization; neurodevelopmental disorders; 1q21.1 syndrome EN chromosome 1 copy number variant array comparative genomic hybridization neurodevelopmental disorders 1q21.1 syndrome 265 273 9 09/07/22 20220701 NES 220701 Conflict of Interest None declared. [21] The DECIPHER database describes several patients with deletions that partially overlap with our patient CNV and sharing several features with our patient, including ID, language impairment, muscular hypotonia, and macrocephaly. [Extracted from the article]

Justyna Miszczyk,1 Mikołaj Przydacz,2 Michał Zembrzuski,2 Piotr L Chłosta2 1Department of Experimental Physics of Complex Systems, The H. Niewodniczański Institute of Nuclear Physics PAN, Krakow, Poland; 2Department of Urology, Jagiellonian University Medical College, Krakow, PolandCorrespondence: Justyna MiszczykDepartment of Experimental Physics of Complex Systems, The H. Niewodniczański Institute of Nuclear Physics PAN, Radzikowskiego 152 Street, Krakow, 31-342, PolandTel +48 126628409Fax +48 126628458Email Justyna.Miszczyk@ifj.edu.plPurpose: Radiotherapy is one of the most common treatments for prostate cancer. Finding a useful predictor of the therapeutic outcome is crucial as it increases the efficacy of treatment planning. This study investigated the individual susceptibility to radiation based on chromosome 1 aberration frequency measured by the FISH (fluorescence in situ hybridization) method.Patients and Methods: Whole blood samples were collected from 27 prostate cancer (PCa) patients and 32 subjects with benign prostatic hyperplasia (BPH), who were considered as a control group. Samples were irradiated with 2 Gy of x-rays, cultured, harvested, and used in the FISH procedure.Results: After irradiation, significantly higher levels of all studied chromosome 1 aberrations (except for deletions) in the group of PCa patients were revealed. Furthermore, in the lymphocytes of cancer patients, nearly five-fold higher frequencies of acentric fragments were observed compared to the BPH group. The highest individual radiosensitivities for all estimated biomarkers were seen in PCa patient cells who reported cancer incidence in the immediate family (CIF+).Conclusion: The differences in chromosome 1 aberrations between PCa and BPH demonstrate that lymphocytes taken from patients with prostate cancer have higher radiosensitivity which might be related to hereditary or familiar inclinations. Therefore, this technique may find future application in searching biomarkers of the cellular radiotherapy response in prostate cancer patients.Keywords: benign prostatic hyperplasia, chromosome 1, prostate cancer, radiotherapy planning, biomarkers, FISH method

Abstract Complete uniparental disomy of chromosome 1 (UPD1) is an uncommon genetic finding about which a specific phenotype has not yet been established. We present a boy who has complete paternal UPD1 and isolated developmental delay and suggest that there is no clear phenotype of UPD1.

Background: Deletion of 1p is associated with poor prognosis in neuroblastoma, however selected 1p-intact patients still experience poor outcomes. Since mutations of 1p genes may mimic the deleterious effects of chromosomal loss, we studied the incidence, spectrum and effects of mutational variants in 1p-intact neuroblastoma. Methods: We characterized the 1p status of 325 neuroblastoma patients, and correlated the mutational status of 1p tumor suppressors and neuroblastoma candidate genes with survival outcomes among 100 1p-intact cases, then performed functional validation of selected novel variants of 1p36 genes identified from our patient cohort. Results: Among patients with adverse disease characteristics, those who additionally had 1p deletion had significantly worse overall survival. Among 100 tumor-normal pairs sequenced, somatic mutations of 1p tumor suppressors KIF1Bβ and CHD5 were most frequent (2%) after ALK and ATRX (8%), and BARD1 (3%). Mutations of neuroblastoma candidate genes were associated with other synchronous mutations and concurrent 11q deletion (P = 0.045). In total, 24 of 38 variants identified were novel and predicted to be deleterious or pathogenic. Functional validation identified novel KIF1Bβ I1355M variant as a gain-of-function mutation with increased expression and tumor suppressive activity, correlating with indolent clinical behavior; another novel variant CHD5 E43Q was a loss-of-function mutation with decreased expression and increased long-term cell viability, corresponding with aggressive disease characteristics. Conclusions: Our study showed that chromosome 1 gene mutations occurred frequently in 1p-intact neuroblastoma, but may not consistently abrogate the function of bonafide 1p tumor suppressors. These findings may augment the evolving model of compounding contributions of 1p gene aberrations toward tumor suppressor inactivation in neuroblastoma. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM), the terminally differentiated B cells malignancy, is widely considered to be incurable since many patients have either developed drug resistance or experienced an eventual relapse. To develop precise and efficient therapeutic strategies, we must understand the pathogenesis of MM. Thus, unveiling the driver events of MM and its further clonal evolution will help us understand this complicated disease. Chromosome 1 instabilities are the most common genomic alterations that participate in MM pathogenesis, and these aberrations of chromosome 1 mainly include copy number variations and structural changes. The chromosome 1q gains/amplifications and 1p deletions are the most frequent structural changes of chromosomes in MM. In this review, we intend to focus on the genes that are affected by chromosome 1 instability: some tumor suppressors were lost or down regulated in 1p deletions, and others that contributed to tumorigenesis were upregulated in 1q gains/amplifications. We have summarized their biological function as well as their roles in the MM pathogenesis, hoping to uncover potential novel therapeutical targets and promote the development of future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Pericentric inversion in chromosome 1 was thought to cause male infertility through spermatogenic impairment, regardless of the breakpoint position. However, carriers of pericentric inversion in chromosome 1 have been reported with normal fertility and familial transmission. Here, we report two cases of pericentric inversion in chromosome 1. One case was detected in utero via amniocentesis, and the other case was detected after the wife of the carrier experienced two spontaneous abortions within 5 years of marriage. Here, the effect of the breakpoint position of the inversion in chromosome 1 on male infertility is examined and compared with the published cases. The association between the breakpoint of pericentric inversion in chromosome 1 and spermatogenesis is also discussed. Overall, the results suggest that the breakpoint position deserves attention from physicians in genetic counseling as inversion carriers can produce offspring.

Background: The occurrence of colorectal cancer (CRC) is increasing among young adults, but the etiology is still largely unknown. In addition to germline monogenetic variants also polygenic risk scores (PRS) have been proven to correctly estimate the risk of CRC., Case Description: We present a 24-year-old male with disseminated colon cancer who carried a germline duplication on chromosome 1 spanning 200 kb and covering CD101, TTF2, MIR942, TRIM45, and parts of PTGFRN and VTCN1 . The duplication was located in tandem. A similar duplication was previously reported in a family with CRC among two brothers aged 52 and 61 years old at diagnosis. Particularly, MIR942 was an interesting finding as it is involved in the regulation of the Wnt signaling pathway. Disruption of the Wnt pathway is known to cause CRC. However, in our case the duplication did not segregate with disease in the family. Calculation of a PRS in our patient found an average PRS for CRC., Conclusions: Our findings do not support that this duplication is a monogenetic cause of CRC, nor did a PRS point towards an increased risk in this 24-year-old male. Whether the duplication is a risk factor in combination with other genetic and non-genetic risk factors requires further studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-148/coif). K.W. reports a speaking engagement at Seagen Denmark ApS for which she received payment. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Rearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynostosis, dysmorphic face, ocular defects, cleft palate, urinary tract anomalies and hand/foot abnormalities. Case presentation: Hereby, we report on an Italian female newborn with craniosynostosis, facial dysmorphisms including bilateral microphthalmia and coloboma, cleft palate, and a severe global developmental and growth delay, associated to a 1p31.3p22.2 deletion of 20.7 Mb. This was inherited from the healthy mother, who was carrier of a smaller (2.6 Mb) deletion included within the centromeric region (1p22.3p22.2) of the same rearrangement, in addition to a translocation between chromosomes 1p and 4q. The deleted region of the proband contains about ninety genes. We focus on the genotype–phenotype correlations. Conclusions: The results of the present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome. It is hard to establish whether the critical rearrangement of such syndrome may involve the centromeric band p22.3p22.2, or more likely do not, also in light of the genomic profile of the healthy mother of our patient. Neonatologists and pediatricians should take into consideration 1p31 microdeletion in cases of developmental and growth delay associated to craniosynostosis, peculiar facial dysmorphisms, cleft palate and hand/foot abnormalities. The present report provides new data about 1p31 microdeletion syndrome, in view of a better characterization of its genomic and phenotypic profile. [ABSTRACT FROM AUTHOR]

Complete uniparental disomy of chromosome 1 (UPD1) is an uncommon genetic finding about which a specific phenotype has not yet been established. We present a boy who has complete paternal UPD1 and isolated developmental delay and suggest that there is no clear phenotype of UPD1. Uniparental disomy of chromosome 1 is not associated with a specific phenotype. It has been associated with diverse recessive disorders where the causative gene is located on chromosome 1. In rare cases, it may be associated with developmental delay. [ABSTRACT FROM AUTHOR]

Polymicrogyria (PMG) is a developmental cortical malformation characterized by an excess of small and frustrane gyration and abnormal cortical lamination. PMG frequently associates with seizures. The molecular pathomechanisms underlying PMG development are not yet understood. About 40 genes have been associated with PMG, and small copy number variations have also been described in selected patients. We recently provided evidence that epilepsy-associated structural brain lesions can be classified based on genomic DNA methylation patterns. Here, we analyzed 26 PMG patients employing array-based DNA methylation profiling on formalin-fixed paraffin-embedded material. A series of 62 well-characterized non-PMG cortical malformations (focal cortical dysplasia type 2a/b and hemimegalencephaly), temporal lobe epilepsy, and non-epilepsy autopsy controls was used as reference cohort. Unsupervised dimensionality reduction and hierarchical cluster analysis of DNA methylation profiles showed that PMG formed a distinct DNA methylation class. Copy number profiling from DNA methylation data identified a uniform duplication spanning the entire long arm of chromosome 1 in 7 out of 26 PMG patients, which was verified by additional fluorescence in situ hybridization analysis. In respective cases, about 50% of nuclei in the center of the PMG lesion were 1q triploid. No chromosomal imbalance was seen in adjacent, architecturally normal-appearing tissue indicating mosaicism. Clinically, PMG 1q patients presented with a unilateral frontal or hemispheric PMG without hemimegalencephaly, a severe form of intractable epilepsy with seizure onset in the first months of life, and severe developmental delay. Our results show that PMG can be classified among other structural brain lesions according to their DNA methylation profile. One subset of PMG with distinct clinical features exhibits a duplication of chromosomal arm 1q. [ABSTRACT FROM AUTHOR]

Chromosome 1q21 aberrations in multiple myeloma have attracted much attention for a long time, however, the prognostic value is still under investigation. We confirmed the independent prognostic impact of 1q21 aberrations in this non-randomized clinical study. Our study noted that additional copies and larger clonal size of 1q21 gain did not worsen the outcome. We discovered that 1q21 gain was associated with the acquisition of new chromosome abnormalities and genomic instability, evidenced by the strong correlation between 1q21 gain and complex karyotypes or the acquisition of more than two cytogenetic aberrations. Moreover, 1q21 gain and/or del(17p) were powerful enough to discriminate high-risk patients. Furthermore, 1q21 gain retained unfavorable even when stratified by concurrent presence of t(4;14), especially in the bortezomib arm. Finally, although bortezomib might benefit patients with 1q21 gain, it could not completely overcome its adverse effects, suggesting the necessity of more effective therapies for these patients. [ABSTRACT FROM AUTHOR]

Cytogenetic studies have shown that human chromosomes 1, 9, and 16, with a large heterochromatic region of highly methylated classical satellite DNA, are prone to induction of chromatid breaks and interchanges by mitomycin C (MMC). A couple of studies have indicated that material from chromosome 9, and possibly also from chromosomes 1 and 16, are preferentially micronucleated by MMC. Here, we further examined the chromosome-specific induction of micronuclei (MN; with and without cytochalasin B) and chromosomal aberrations (CAs) by MMC. Cultures of isolated human lymphocytes from two male donors were treated (at 48 h of culture, for 24 h) with MMC (500 ng/ml), and the induced MN were examined by a pancentromeric DNA probe and paint probe for chromosome 9, and by paint probes for chromosomes 1 and 16. MMC increased the total frequency of MN by 6–8-fold but the frequency of chromosome 9 -positive (9+) MN by 29–30-fold and the frequency of chromosome 1 -positive (1+) MN and chromosome 16 -positive (16+) MN by 12–16-fold and 10–17-fold, respectively. After treatment with MMC, 34–47 % of all MN were 9+, 17–20 % 1+, and 3–4 % 16+. The majority (94–96 %) of the 9+ MN contained no centromere and thus harboured acentric fragments. When MMC-induced CAs aberrations were characterized by using the pancentromeric DNA probe and probes for the classical satellite region and long- and short- arm telomeres of chromosome 9, a high proportion of chromosomal breaks (31 %) and interchanges (41 %) concerned chromosome 9. In 83 % of cases, the breakpoint in chromosome 9 was just below the region (9cen-q12) labelled by the classical satellite probe. Our results indicate that MMC specifically induces MN harbouring fragments of chromosome 9, 1, and 16. CAs of chromosome 9 are highly overrepresented in metaphases of MMC-treated lymphocytes. The preferential breakpoint is below the region 9q12. • Mitomycin C-induced human micronuclei and chromosome aberrations were characterized. • Fluorescence in situ hybridization and chromosome paints in human lymphocytes were used. • Chromosomes 9, 1 and 16 are over-represented in induced micronuclei. • Chromosome 9 is highly involved in induced chromatid breaks and exchanges. • The preferential breakpoint in chromosome 9 is right below long arm band 9cen-q12. [ABSTRACT FROM AUTHOR]

Various anomalies of chromosome 1 which is the largest chromosome of the human karyotype were found in various hematologic diseases. In this retrospective study, clinical features and cytogenetic anomalies of 35 hematological patients with various chromosome 1 anomalies were correlated. Also the effect of chromosome 1 anomalies to the disease prognosis of those patients was discussed. Conventional cytogenetic analysis of those patients was performed by investigating metaphases of 24 hours stimulated bone marrow samples. After cell culturing, the samples were treated with trypsin and stained with Giemsa (GTG Banding). Analyses were performed on image analysis system. Chromosome 1 anomalies were determined in 35 patients (0.5 %) among 6865 samples having done their conventional bone marrow cytogenetic analysis in our center between January 2008 and March 2016. The ratio of chromosome 1 anomalies of totally 701 anomalies among 6865 patients was 4.9%. Chromosome 1 anomalies were found mostly in patients with Multiple Myeloma (MM), Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) in our study group. The most common anomaly was deletion 1 which was seen in 16 (37%) patients. Second most common anomaly was derivation 1 which was seen in 13 (30%) patients. Also translocations between chromosome 1 and other chromosomes were observed. The genetic aberration formed as a result of chromosomal anomalies result in the formation of hematologic malignancies. The effect on disease pathogenesis and prognosis of some of those anomalies are unknown and have to be investigated and determined.

Pericentric inversion in chromosome 1 was thought to cause male infertility through spermatogenic impairment, regardless of the breakpoint position. However, carriers of pericentric inversion in chromosome 1 have been reported with normal fertility and familial transmission. Here, we report two cases of pericentric inversion in chromosome 1. One case was detected in utero via amniocentesis, and the other case was detected after the wife of the carrier experienced two spontaneous abortions within 5 years of marriage. Here, the effect of the breakpoint position of the inversion in chromosome 1 on male infertility is examined and compared with the published cases. The association between the breakpoint of pericentric inversion in chromosome 1 and spermatogenesis is also discussed. Overall, the results suggest that the breakpoint position deserves attention from physicians in genetic counseling as inversion carriers can produce offspring. [ABSTRACT FROM AUTHOR]

Various anomalies of chromosome 1 which is the largest chromosome of the human karyotype were found in various hematologic diseases. In this retrospective study, clinical features and cytogenetic anomalies of 35 hematological patients with various chromosome 1 anomalies were correlated. Also the effect of chromosome 1 anomalies to the disease prognosis of those patients was discussed. Conventional cytogenetic analysis of those patients was performed by investigating metaphases of 24 hours stimulated bone marrow samples. After cell culturing, the samples were treated with trypsin and stained with Giemsa (GTG Banding). Analyses were performed on image analysis system. Chromosome 1 anomalies were determined in 35 patients (0.5%) among 6865 samples having done their conventional bone marrow cytogenetic analysis in our center between January 2008 and March 2016. The ratio of chromosome 1 anomalies of totally 701 anomalies among 6865 patients was 4.9%. Chromosome 1 anomalies were found mostly in patients with Multiple Myeloma (MM), Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) in our study group. The most common anomaly was deletion 1 which was seen in 16 (37%) patients. Second most common anomaly was derivation 1 which was seen in 13 (30%) patients. Also translocations between chromosome 1 and other chromosomes were observed. The genetic aberration formed as a result of chromosomal anomalies result in the formation of hematologic malignancies. The effect on disease pathogenesis and prognosis of some of those anomalies are unknown and have to be investigated and determined. [ABSTRACT FROM AUTHOR]

The promyelocytic leukemia (PML)-retinoic acid receptor α (RARA) fusion is hypothesized to serve a vital role in the pathogenesis of acute promyelocytic leukemia (APL), which results from a reciprocal translocation between chromosomes 15 and 17, t(15;17)(q24;q21). A minority of APL cases lack the classical t(15;17) and have been identified to have cryptic or masked t(15;17) or complex translocations. The present study reports on a case of a 37-year-old male with APL harboring a complex three-way translocation t(1;17;15)(q21;q21;q24). This karyotypic interpretation was further confirmed by fluorescence in situ hybridization, and 98% of the bone marrow cells analyzed were positive for the PML-RARA fusion gene. After combined treatment with all-trans retinoic acid and arsenic trioxide, the patient achieved complete remission with no recurrence for 3 years to date. To the best of our knowledge, the present study is the first to report on the novel variant of t(15;17) involving the breakpoint 1q21. [ABSTRACT FROM AUTHOR]

The deletion of the distal long arm of chromosome 1 is associated with a characteristic facial appearance and a pattern of associated malformations. Characteristic manifestations include a round face with prominent 'cupid's bow' and downturned corners of the mouth, thin vermilion borders of lips, a long upper lip with a smooth philtrum, a short and broad nose, epicanthal folds, apparently low-set ears, micrognathia, microcephaly, abnormal hands and feet, variable cardiac or genital anomalies, moderate to severe mental retardation, and growth retardation. Using fluorescent in situ hybridization (FISH) analysis to map precisely the deletion, we present a case of chromosome 1q44 deletion with craniofacial characteristics, multiple congenital anomalies, and growth and psychomotor retardation. In comparison with other reported cases of 1q43-44 deletion, the subject does not show hydrocephalus, seizure, syn- or polydactyly of hands, and a urogenital anomaly. However, an arachnoid cyst, pinpoint dimple on the midline of the forehead, a right-sided supernumerary nipple and auricular pit, polydactyly of the right foot, adducted thumb, and flexion restriction of the proximal interphalangeal joint with a simian line in both hands were observed additionally.

Rearrangements of the region 1q42.13q43 are rare, with only 7 cases reported to date. The imbalances described are usually the result of inherited translocations with other chromosomes. Moreover, few cases of both inter- and intrachromosomal deletions/duplications detected cytogenetically have been described. We report the molecular cytogenetic characterization of an inverted insertion involving the region 1q42.13q43 and segregating in 2 generations of a family. The deletion and the duplication of the same segment were detected in 2 affected family members. SNP array analysis showed the familial origin of the deletion/duplication due to the occurrence of a crossing-over during meiosis. Our report underlines the importance of determining the correct origin of chromosomal aberrations using different molecular cytogenetic tests in order to provide a good estimation of the reproductive risk for the members of the family. [ABSTRACT FROM AUTHOR]

Methylation of cytosine at the 5 position of the pyrimidine ring is the most prevalent and significant epigenetic modifications in mammalian DNA. The CpG methylation level shows a bimodal distribution but the bimodality can be overestimated due to the heterogeneity of per-base depth. Here, we developed an algorithm to eliminate the effect of per-base depth inhomogeneity on the bimodality and obtained a random CpG methylation distribution. By quantifying the deviation of the observed methylation distribution and the random one using the information formula, we find that in tetranucleotides 5’-N5CGN3-3’ (N5, N3 = A, C, G or T), GCGN3 and CCGN3 show less apparent deviation than ACGN3 and TCGN3, indicating that GCGN3 and CCGN3 are less variant in their level of methylation. The methylation variation of N5CGN3 are conserved among different cells, tissues and species, implying common features in the mechanisms of methylation and demethylation, presumably mediated by DNMTs and TETs in mammalians, respectively. Sequence dependence of DNA methylation variation also relates to gene regulatory and promotes the reexamination of the role of DNA sequence in fundamental biological processes. [ABSTRACT FROM AUTHOR]

Both natural and artificial selection play a critical role in animals' adaptation to the environment. Detection of the signature of selection in genomic regions can provide insights for understanding the function of specific phenotypes. It is generally assumed that laboratory mice may experience intense artificial selection while wild mice more natural selection. However, the differences of selection signature in the mouse genome and underlying genes between wild and laboratory mice remain unclear. In this study, we used two mouse populations: chromosome 1 (Chr 1) substitution lines (C1SLs) derived from Chinese wild mice and mouse genome project (MGP) sequenced inbred strains and two selection detection statistics: Fst and Tajima's D to identify the signature of selection footprint on Chr 1. For the differentiation between the C1SLs and MGP, 110 candidate selection regions containing 47 protein coding genes were detected. A total of 149 selection regions which encompass 7.215 Mb were identified in the C1SLs by Tajima's D approach. While for the MGP, we identified nearly twice selection regions (243) compared with the C1SLs which accounted for 13.27 Mb Chr 1 sequence. Through functional annotation, we identified several biological processes with significant enrichment including seven genes in the olfactory transduction pathway. In addition, we searched the phenotypes associated with the 47 candidate selection genes identified by Fst. These genes were involved in behavior, growth or body weight, mortality or aging, and immune systems which align well with the phenotypic differences between wild and laboratory mice. Therefore, the findings would be helpful for our understanding of the phenotypic differences between wild and laboratory mice and applications for using this new mouse resource (C1SLs) for further genetics studies. [ABSTRACT FROM AUTHOR]

Glutathione (GSH) production during wine fermentation is a desirable trait as it can limit must and wine oxidation and protect various aromatic compounds. UMCC 2581 is a Saccharomyces cerevisiae wine strain with enhanced GSH content at the end of wine fermentation. This strain was previously derived by selection for molybdate resistance following a sexual cycle of UMCC 855 using an evolution-based strategy. In this study, we examined genetic and gene expression changes associated with the derivation of UMCC 2581. For genetic analysis we sporulated the diploid UMCC 855 parental strain and found four phenotype classes of segregants related to molybdate resistance, demonstrating the presence of segregating variation from the parental strain. Using bulk segregant analysis we mapped molybdate traits to two loci. By sequencing both the parental and evolved strain genomes we identified candidate mutations within the two regions as well as an extra copy of chromosome 1 in UMCC 2581. Combining the mapped loci with gene expression profiles of the evolved and parental strains we identified a number of candidate genes with genetic and/or gene expression changes that could underlie molybdate resistance and increased GSH levels. Our results provide insight into the genetic basis of GSH production relevant to winemaking and highlight the value of enhancing wine strains using existing variation present in wine strains. [ABSTRACT FROM AUTHOR]

To compensate for the sex difference in the number of X chromosomes, human females, like human males have only one active X. The other X chromosomes in cells of both sexes are silenced in utero by XIST, the Inactive X Specific Transcript gene, that is present on all X chromosomes. To investigate the means by which the human active X is protected from silencing by XIST, we updated the search for a key dosage sensitive XIST repressor using new cytogenetic data with more precise resolution. Here, based on a previously unknown sex bias in copy number variations, we identify a unique region in our genome, and propose candidate genes that lie within, as they could inactivate XIST. Unlike males, the females who duplicate this region of chromosome 19 (partial 19 trisomy) do not survive embryogenesis; this preimplantation loss of females may be one reason that more human males are born than females. [ABSTRACT FROM AUTHOR]

Salinity is a major threat to rice production worldwide. Several studies have been conducted to elucidate the molecular basis of salinity tolerance in rice. However, the genetic information such as quantitative trait loci (QTLs) and molecular markers, emanating from these studies, were rarely exploited for marker-assisted breeding. To better understand salinity tolerance and to validate previously reported QTLs at seedling stage, a set of introgression lines (ILs) of a salt tolerant donor line ‘Pokkali’ developed in a susceptible high yielding rice cultivar ‘Bengal’ background was evaluated for several morphological and physiological traits under salt stress. Both SSR and genotyping-by-sequencing (GBS) derived SNP markers were utilized to characterize the ILs and identify QTLs for traits related to salinity tolerance. A total of eighteen and thirty-two QTLs were detected using SSR and SNP markers, respectively. At least fourteen QTLs detected in the RIL population developed from the same cross were validated in IL population. Analysis of phenotypic responses, genomic composition, and QTLs present in the tolerant ILs suggested that the mechanisms of tolerance could be Na+ dilution in leaves, vacuolar Na+ compartmentation, and possibly synthesis of compatible solutes. Our results emphasize the use of salt injury score (SIS) QTLs in marker-assisted breeding to improve salinity tolerance. The tolerant lines identified in this study will serve as improved breeding materials for transferring salinity tolerance without the undesirable traits of Pokkali. Additionally, the lines will be useful for fine mapping and map-based cloning of genes responsible for salinity tolerance. [ABSTRACT FROM AUTHOR]

Understanding the mechanisms responsible for phenotypic diversification within and among species ultimately rests with linking naturally occurring mutations to functionally and ecologically significant traits. Colour polymorphisms are of great interest in this context because discrete colour patterns within a population are often controlled by just a few genes in a common environment. We investigated how and why phenotypic diversity arose and persists in the Zosterops borbonicus white-eye of Reunion (Mascarene archipelago), a colour polymorphic songbird in which all highland populations contain individuals belonging to either a brown or a grey plumage morph. Using extensive phenotypic and genomic data, we demonstrate that this melanin-based colour polymorphism is controlled by a single locus on chromosome 1 with two large-effect alleles, which was not previously described as affecting hair or feather colour. Differences between colour morphs appear to rely upon complex cis-regulatory variation that either prevents the synthesis of pheomelanin in grey feathers, or increases its production in brown ones. We used coalescent analyses to show that, from a ‘brown’ ancestral population, the dominant ‘grey’ allele spread quickly once it arose from a new mutation. Since colour morphs are always found in mixture, this implies that the selected allele does not go to fixation, but instead reaches an intermediate frequency, as would be expected under balancing selection.

Objective: To present prenatal diagnosis and molecular cytogenetic characterization of de novo partial monosomy 1p (1p36.23→pter) and partial trisomy 20p (20p12.1→pter) associated with ventriculomegaly, ventricular septal defect and midface hypoplasia. Materials, Methods and Results: A 31-year-old, primigravid woman was referred for amniocentesis at 20 gestational weeks because of ventriculomegaly, ventricular septal defect, and midface hypoplasia. Amniocentesis revealed an aberrant derivative chromosome 1, or der(1). Parental karyotypes were normal. Spectral karyotyping analysis revealed that the der(1) contained a segment of chromosome 20 in the distal end of the short arm of chromosome 1. Array comparative genomic hybridization demonstrated an 8.4-Mb distal 1p deletion and a 14-Mb distal 20p duplication. The karyotype was 46,XX,der(1)t(1;20)(p36.23;p12.1)dn. Polymorphic DNA marker analysis determined the paternal origin of the aberrant chromosome. The pregnancy was subsequently terminated. A 462-g malformed female fetus was delivered at 22 gestational weeks with a prominent forehead, midface hypoplasia, a flat nasal bridge, low-set ears, a long philtrum, a pointed chin and micrognathia. Conclusion: Spectral karyotyping, fluorescence in situ hybridization and array comparative genomic hybridization are useful for the prenatal investigation of the nature of a de novo aberrant derivative chromosome. Partial monosomy 1p (1p36.23→pter) and partial trisomy 20p (20p12.1→pter) are associated with ventriculomegaly, ventricular septal defect and midface hypoplasia on prenatal ultrasound. Prenatal diagnosis of ventriculomegaly, congenital heart defects and midface hypoplasia should alert clinicians to chromosome 1p36 deletion syndrome and prompt molecular cytogenetic analysis if necessary.

The extent of epigenetic variation is currently well documented, but the number of natural epialleles described so far remains very limited. Determining the relevance of epigenetic changes for natural variation is an important question of research that we investigate by isolating natural epialleles segregating in Arabidopsis recombinant populations. We previously described a genetic incompatibility among Arabidopsis strains based on the silencing of a gene involved in fitness. Here, we isolated a new epiallele resulting from the silencing of a transfer-RNA editing gene in an Arabidopsis accession from the Netherlands (Nok-1). Crosses with the reference accession Col-0 show a complete incompatibility between this epiallele and another locus localized on a different chromosome. We demonstrate that conversion of an unmethylated version of this allele occurs in hybrids, associated with modifications of small RNA populations. These epialleles can also spontaneously revert within the population. Furthermore, we bring evidence that neither METHYLTRANSFERASE 1, maintaining methylation at CGs, nor components of RNA-directed DNA methylation, are key factors for the transmission of the epiallele over generations. This depends only on the self-reinforcing loop between CHROMOMETHYLASE 3 and KRYPTONITE, involving DNA methylated in the CHG context and histone H3 lysine 9 methylation. Our findings reveal a predominant role of this loop in maintaining a natural epiallele. [ABSTRACT FROM AUTHOR]

The natural restoration of soils polluted by aromatic hydrocarbons such as benzene, toluene, ethylbenzene and m- and p-xylene (BTEX) may be accelerated by inoculation of specific biodegraders (bioaugmentation). Bioaugmentation mainly involves introducing bacteria that deploy their metabolic properties and adaptation potential to survive and propagate in the contaminated environment by degrading the pollutant. In order to better understand the adaptive response of cells during a transition to contaminated material, we analyzed here the genome and short-term (1 h) changes in genome-wide gene expression of the BTEX-degrading bacterium Pseudomonas veronii 1YdBTEX2 in non-sterile soil and liquid medium, both in presence or absence of toluene. We obtained a gapless genome sequence of P. veronii 1YdBTEX2 covering three individual replicons with a total size of 8 Mb, two of which are largely unrelated to current known bacterial replicons. One-hour exposure to toluene, both in soil and liquid, triggered massive transcription (up to 208-fold induction) of multiple gene clusters, such as toluene degradation pathway(s), chemotaxis and toluene efflux pumps. This clearly underlines their key role in the adaptive response to toluene. In comparison to liquid medium, cells in soil drastically changed expression of genes involved in membrane functioning (e.g., lipid composition, lipid metabolism, cell fatty acid synthesis), osmotic stress response (e.g., polyamine or trehalose synthesis, uptake of potassium) and putrescine metabolism, highlighting the immediate response mechanisms of P. veronii 1YdBTEX2 for successful establishment in polluted soil. [ABSTRACT FROM AUTHOR]

Interstitial deletions of the long arm of chromosome 1 are rare, and recent reports of individuals with molecularly characterized deletions have resulted in advances in genotype-phenotype correlation. The recognizable phenotype associated with 1q23.3-q25.1 includes pre- and post-natal growth retardation, microcephaly, intellectual disability, delayed language acquisition, small hands and feet with brachydactyly and single palmar crease, and distinctive facial features including short bulbous nose, micrognathia, and ear malformations. We report a patient with an 11.35 Mb deletion from 1q23.3-q25.1 who has these features in addition to a rarely reported complication-profound sensorineural hearing loss. He has both pre- and post-natal growth deficiency and growth hormone deficiency that was diagnosed at age 2 years. However, unlike other individuals with this deletion and growth hormone deficiency, this boy has responded to treatment with human growth hormone. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A basic goal in the development of recombinant proteins is the generation of cell lines that express the desired protein stably over many generations. Here, we constructed engineered Chinese hamster ovary cell lines (CHO-S) with a pCHO-hVR1 vector that carried an extracellular domain of a VEGF receptor (VR) fusion gene. Forty-five clones with high hVR1 expression were selected for karyotype analysis. Using fluorescence in situ hybridization (FISH) and G-banding, we found that pCHO-hVR1 was integrated into three chromosomes, including chromosomes 1, Z3 and Z4. Four clones were selected to evaluate their productivity under non-fed, non-optimized shake flask conditions. The results showed that clones 1 and 2 with integration sites on chromosome 1 revealed high levels of hVR1 products (shake flask of approximately 800 mg/L), whereas clones 3 and 4 with integration sites on chromosomes Z3 or Z4 had lower levels of hVR1 products. Furthermore, clones 1 and 2 maintained their productivity stabilities over a continuous period of 80 generations, and clones 3 and 4 showed significant declines in their productivities in the presence of selection pressure. Finally, pCHO-hVR1 localized to the same region at chromosome 1q13, the telomere region of normal chromosome 1. In this study, these results demonstrate that the integration of exogenous hVR1 gene on chromosome 1, band q13, may create a high protein-producing CHO-S cell line, suggesting that chromosome 1q13 may contain a useful target site for the high expression of exogenous protein. This study shows that the integration into the target site of chromosome 1q13 may avoid the problems of random integration that cause gene silencing or also overcome position effects, facilitating exogenous gene expression in CHO-S cells. [ABSTRACT FROM AUTHOR]

Aberrant DNA methylation is a frequent epigenetic alteration in cancer cells that has emerged as a pivotal mechanism for tumorigenesis. Accordingly, novel therapies targeting the epigenome are being explored with the aim to restore normal DNA methylation patterns on oncogenes and tumor suppressor genes. A limited number of studies indicate that dietary compound resveratrol modulates DNA methylation of several cancer-related genes; however a complete view of changes in methylome by resveratrol has not been reported yet. In this study we performed a genome-wide survey of DNA methylation signatures in triple negative breast cancer cells exposed to resveratrol. Our data showed that resveratrol treatment for 24 h and 48 h decreased gene promoter hypermethylation and increased DNA hypomethylation. Of 2476 hypermethylated genes in control cells, 1,459 and 1,547 were differentially hypomethylated after 24 h and 48 h, respectively. Remarkably, resveratrol did not induce widespread non-specific DNA hyper- or hypomethylation as changes in methylation were found in only 12.5% of 27,728 CpG loci. Moreover, resveratrol restores the hypomethylated and hypermethylated status of key tumor suppressor genes and oncogenes, respectively. Importantly, the integrative analysis of methylome and transcriptome profiles in response to resveratrol showed that methylation alterations were concordant with changes in mRNA expression. Our findings reveal for the first time the impact of resveratrol on the methylome of breast cancer cells and identify novel potential targets for epigenetic therapy. We propose that resveratrol may be considered as a dietary epidrug as it may exert its anti-tumor activities by modifying the methylation status of cancer -related genes which deserves further in vivo characterization. [ABSTRACT FROM AUTHOR]

Aedes aegypti, the primary vector of dengue, yellow fever and Zika flaviviruses, consists of at least two subspecies. Aedes aegypti (Aaa) is light in color, has pale scales on the first abdominal tergite, oviposits in artificial containers, and preferentially feeds on humans. Aedes aegypti formosus (Aaf), has a dark cuticle, is restricted to sub-Saharan Africa, has no pale scales on the first abdominal tergite and frequently oviposits in natural containers. Scale patterns correlate with cuticle color in East Africa but not in Senegal, West Africa where black cuticle mosquitoes display a continuum of scaling patterns and breed domestically indoors. An earlier laboratory study did not indicate any pre- or postzygotic barriers to gene flow between Aaa and Aaf in East Africa. However, similar attempts to construct F1 intercross families between Aaa laboratory strains and Senegal Ae. aegypti (SenAae) failed due to poor F1 oviposition and low F2 egg-to-adult survival. Insemination and assortative mating experiments failed to identify prezygotic mating barriers. Backcrosses were performed to test for postzygotic isolation patterns consistent with Haldane’s rule modified for species, like Aedes, that have an autosomal sex determining locus (SDL). Egg-pupal survival was predicted to be low in females mated to hybrid F1 males but average when a male mates with a hybrid F1 female. Survival was in fact significantly reduced when females mated to hybrid males but egg-pupal survival was significantly increased when males were mated to hybrid F1 females. These observations are therefore inconclusive with regards to Haldane’s rule. Basic cytogenetic analyses and Fluorescent In Situ Hybridization (FISH) experiments were performed to compare SenAae strains with the IB12 strain of Aaa that was used for genome sequencing and physical mapping. Some SenAae strains had longer chromosomes than IB12 and significantly different centromeric indices on chromosomes 1 and 3. DAPI staining was used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere) inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3. [ABSTRACT FROM AUTHOR]

Key Clinical Message We present a male patient with constitutional ring 1 chromosome and subsequent 6 Mb deletion at 1q43q44. The patient displays overlapping clinical features with reported patients with ring 1 chromosome and 1q43q44 microdeletion syndrome. To our knowledge, this is the first patient with ring 1 chromosome characterized by comparative genomic hybridization. [ABSTRACT FROM AUTHOR]

The genetic factors underlying changes in ear morphology, and particularly the inheritance of kernel row number (KRN), have been broadly investigated in diverse mapping populations in maize (Zea mays L.). In this study, we mapped a region on the long arm of chromosome 1 containing a QTL for KRN. This work was performed using a set of ecombinant hromosome early sogenic ines (RCNILs) derived from a BC2S3 population produced using the inbred maize line W22 and teosinte (Zea mays ssp. parviglumis) as the parents. A set of 48 RCNILs was evaluated in the field during the summer of 2013 in order to perform the mapping. A QTL for KRN was found that explained approximately 51% of the phenotypic variance and had a 1.5-LOD confidence interval of 203 kb. Seven genes are described in this interval. One of these candidate genes may have been the target of domestication processes in maize and contributed to the shift from two kernel row ears in teosinte to a highly polystichous ear in maize. [ABSTRACT FROM AUTHOR]

Background: There is still an open question how to predict colorectal cancer risk before any morphological changes appear in the colon. Objective: The purpose was to investigate aberrations in chromosomes 1, 2 and 4 in peripheral blood lymphocytes analyzed by fluorescence in situ hybridization technique as a tool to assess the likelihood of colorectal cancer. Methods: A hospital-based case-control study included 20 colon cancer patients and 18 hospital-based controls. Information about potential covariates was collected by interview. The frequency of stable and unstable chromosome aberrations in chromosome 1, 2 and 4 was assessed by fluorescence in situ hybridization technique. Results: Colorectal cancer patients, as compared to controls, had a relatively higher frequency of chromosome 1 translocations (median: 3.5 versus 1.0 /1000 cells, p = 0.006), stable aberrations (3.8 versus 1.0 /1000 cells, p = 0.007) and total aberrations (p = 0.009). There were no differences observed for chromosomes 2 and 4. Our results showed an increase in the odds of having colon cancer by about 50–80% associated with an increase by 1/1000 cells in the number of chromosome 1 aberrations. Conclusions: The results revealed that the frequency of chromosomal aberrations, especially translocations in chromosome 1, seems to be a promising method to show a colon cancer risk. Additionally, our study suggests the reasonableness of use of biomarkers such as chromosome 1 aberrations in peripheral blood lymphocytes in screening prevention programs for individuals at higher colon cancer risk to identify those who are at increased risk and require more frequent investigations, e.g. by sigmoidoscopy. [ABSTRACT FROM AUTHOR]

The present study aimed at investigating genetic variations, specific signal pathways, or biological processes of chromosome 1 genes between subtypes and stages of lung cancer and prediction of selected targeting genes for patient survival rate. About 537 patients with lung adenocarcinoma (ADC), 140 with lung squamous carcinoma (SCC), 9 with lung large-cell carcinoma (LCC), 56 with small-cell lung cancer (SCLC), and 590 without caner were integrated from 16 databases and analyzed in the present study. Three ( ASPM, CDC20, KIAA1799) or 28 genes significantly up- or down-expressed in four subtypes of lung cancer. The activated cell division and down-regulated immune responses were identified in patients with lung cancer. Keratinocyte development associated genes S100 and SPRR families dominantly up-expressed in SCC and AKT3 and NRAS in SCLC. Subtype-specific genes of ADC, SCC, LCC, or SCLC were also identified. C1orf106, CAPN8, CDC20, COL11A1, CRABP2, and NBPF9 up-expressed at four stages of ADC. Fifty six related with keratinocytes or potassium channels up-expressed in three stages of SCC. CDC20, IL10, ECM1, GABPB2, CRABP2, and COL11A1 significantly predicted the poor overall survival of ADC patients and S100A2 and TIMM17A in SCC patients. Our data indicate that a number of altered chromosome 1 genes have the subtype and stage specificities of lung cancer and can be considered as diagnostic and prognosis biomarkers. [ABSTRACT FROM AUTHOR]

Inversion occurs after two breaks in a chromosome have happened and the segment rotates 180° before reinserting. Inversion carriers have produced abnormal gametes if there is an odd number crossing- over between the inverted and the normal homologous chromosomes causing a duplication or deletion. Reproductive risks such as infertility, abortion, stillbirth and birth of malformed child would be expected in that case. A 54-year-old male patient was consulted to our clinic for primary infertility. The routine chromosome study were applied using peripheral blood lymphocyte cultures and analyzed by giemsa-trypsingiemsa (GTG) banding, and centromer banding (C-banding) stains. Y chromosome microdeletions in the azoospermia factor (AZF) regions were analyzed with polymerase chain reaction. Additional test such as fluorescence in situ hybridization (FISH) was used to detect the sex-determining region of the Y chromosome (SRY). Semen analysis showed azoospermia. A large pericentric inversion of chromosome 1 46,XY, inv(1) (p22q32) was found in routine chromosome analysis. No microdeletions were seen in AZF regions. In our patient the presence of SRY region was observed by using FISH technique with SRY-specific probe. Men who have pericentric inversion of chromosome 1, appear to be at risk for infertility brought about by spermatogenic breakdown. The etiopathogenic relationship between azoospermia and pericentric inversion of chromosome 1 is discussed. [ABSTRACT FROM AUTHOR]

Introduction: deletion of long arm of chromosome 1(1q-) is a rare condition. Clinical features include Dwarfism, severe mental retardation, microcephaly and short neck delineating the "intermediate 1q deletion syndrome". Case Report: we report a new case of interstitial deletion of the long arm of chromosome 1, diagnosed in a 22+3 weeks gestation fetus in which cytogenetic analysis localized a loss of genetic materials of 18Mb in the 1q25.3-32.1. Fetal ultrasound showed neurodegenerative defects resembling Dandy-Walker's syndrome and bilateral clubfoot. Conclusions: clinical characteristics of our case are markedly mild. This suggests that the type and the extension of the mutation obtained through cytogenetic studies, CGH array and ultrasound evaluation should be taken into account for prognostic evaluation and management of these patients. [ABSTRACT FROM AUTHOR]