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Background: Intellectual disability is a prevalent neurodevelopmental disorder, with the majority of affected children exhibiting global developmental delay before the age of 5 years. In recent years, certain children have been found to carry homozygous variations of the EEF1D gene, leading to autosomal recessive intellectual disability. However, the pathogenicity of compound heterozygous variations in this gene remains largely unknown., Methods: Trio whole-exome sequencing and copy number variation sequencing were done for the genetic etiological diagnosis of a 3-year and 11-month-old Chinese boy who presented with brachycephaly, severe to profound global developmental delay, and hypotonia in the lower limbs., Results: In this case, compound heterozygous variants of the EEF1D gene were found in the child through trio whole-exome sequencing; one was a splice variant (NM_032378.6:c.1905+1G>A) inherited from his father, and the other was a nonsense variant (NM_032378.6:c.676C>T) inherited from his mother. The nonsense variant leads to the production of a premature termination (p.Gln226*). These variations have the ability to explain the clinical phenotypes of the child., Conclusions: Our study expands the variation spectrum and provides compelling evidence for EEF1D as a candidate gene for autosomal recessive intellectual disability. However, due to the deficient number of reported cases, researchers need to further study EEF1D and supplement the clinical phenotypes and treatment measures., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Triploid Populus tomentosa, a timber tree species, has been widely planted in northern China owing to its potential high yields and high wood quality. Though genetic variances in growth traits and wood properties have been reported across several planting sites, regional testing of triploid hybrid clones of P. tomentosa has not been conducted on a large scale., Results: Ten 5-year clonal trials were used to evaluate the inheritance of growth traits, to determine suitable deployment zones, and to identify optimal triploid clones at each experimental site to determine the clones that would be suitable at all sites. A total of 2,430 trees from nine triploid hybrid clones were sampled during the ten trials. The clonal and site effects and clone × site interactions were highly significant (P < 0.001) for all the studied growth and yield traits. The estimated repeatability of means for diameter at breast height (DBH) and tree height (H) was 0.83, which was slightly higher than for stem volume (SV) and estimated stand volume (ESV) (0.78). The Weixian (WX), Gaotang (GT), and Yanzhou (YZ) sites were each considered to be suitable deployment zones, and the Zhengzhou (ZZ), Taiyuan (TY), Pinggu (PG), and Xiangfen (XF) sites were found to be the optimal deployment zones. The TY and ZZ sites were the best discriminative environments, and the GT and XF sites were the best representative environments. GGE pilot analysis revealed that yield performance and stability were significantly different among all the studied triploid hybrid clones across the ten test sites. It was therefore necessary to develop a suitable triploid hybrid clone that could do well at each site. Taking into account both yield performance and stability, the triploid hybrid clone S2 was determined to be an ideal genotype., Conclusions: For triploid hybrid clones, the WX, GT, and YZ sites represented suitable deployment zones and the ZZ, TY, PG, and XF sites represented optimal deployment zones. Yield performance and stability were significantly different among all the studied triploid hybrid clones across the ten test sites. Developing a suitable triploid hybrid clone that could do well at all sites was therefore desirable., (© 2023. The Author(s).)

Background: Currently, diabetes has become one of the leading causes of death worldwide. Fasting plasma glucose (FPG) levels that are higher than optimal, even if below the diagnostic threshold of diabetes, can also lead to increased morbidity and mortality. Here we intend to study the magnitude of the genetic influence on FPG variation by conducting structural equation modelling analysis and to further identify specific genetic variants potentially related to FPG levels by performing a genome-wide association study (GWAS) in Chinese twins., Results: The final sample included 382 twin pairs: 139 dizygotic (DZ) pairs and 243 monozygotic (MZ) pairs. The DZ twin correlation for the FPG level (r DZ  = 0.20, 95% CI: 0.04-0.36) was much lower than half that of the MZ twin correlation (r MZ  = 0.68, 95% CI: 0.62-0.74). For the variation in FPG level, the AE model was the better fitting model, with additive genetic parameters (A) accounting for 67.66% (95% CI: 60.50-73.62%) and unique environmental or residual parameters (E) accounting for 32.34% (95% CI: 26.38-39.55%), respectively. In the GWAS, although no genetic variants reached the genome-wide significance level (P < 5 × 10 - 8 ), 28 SNPs exceeded the level of a suggestive association (P < 1 × 10 - 5 ). One promising genetic region (2q33.1) around rs10931893 (P = 1.53 × 10 - 7 ) was found. After imputing untyped SNPs, we found that rs60106404 (P = 2.38 × 10 - 8 ) located at SPATS2L reached the genome-wide significance level, and 216 SNPs exceeded the level of a suggestive association. We found 1007 genes nominally associated with the FPG level (P < 0.05), including SPATS2L, KCNK5, ADCY5, PCSK1, PTPRA, and SLC26A11. Moreover, C1orf74 (P = 0.014) and SLC26A11 (P = 0.021) were differentially expressed between patients with impaired fasting glucose and healthy controls. Some important enriched biological pathways, such as β-alanine metabolism, regulation of insulin secretion, glucagon signaling in metabolic regulation, IL-1 receptor pathway, signaling by platelet derived growth factor, cysteine and methionine metabolism pathway, were identified., Conclusions: The FPG level is highly heritable in the Chinese population, and genetic variants are significantly involved in regulatory domains, functional genes and biological pathways that mediate FPG levels. This study provides important clues for further elucidating the molecular mechanism of glucose homeostasis and discovering new diagnostic biomarkers and therapeutic targets for diabetes.

Background: Social attention ability is crucial for human adaptive social behaviors and interpersonal communications, and the malfunction of which has been implicated in autism spectrum disorder (ASD), a highly genetic neurodevelopmental disorder marked by striking social deficits., Methods: Using a classical twin design, the current study investigated the genetic contribution to individual variation in social and non-social attention abilities, and further probed their potential genetic linkage. Moreover, individual autistic traits were further measured in an independent group of non-twin participants to examine the hypothetical link between the core social attention ability and ASD., Results: We found reliable genetic influences on the social attentional effects induced by two distinct cues (eye gaze and walking direction), with 91% of their covariance accounted for by common genetic effects. However, no evidence of heritability or shared genetic effects was observed for the attentional effect directed by a non-social cue (i.e. arrow direction) and its correlation with the social attention ability. Remarkably, one's autistic traits could well predict his/her heritable core social attention ability extracted from the conventional social attentional effect., Conclusions: These findings together suggest that human social attention ability is supported by unique genetic mechanisms that can be shared across different social, but not non-social, processing. Moreover, they also encourage the identification of 'social attention genes' and highlight the critical role of the core human social attention ability in seeking the endophenotypes of social cognitive disorders including ASD.

A multi-trait selective breeding program of Macrobrachium rosenbergii was initiated in China in 2015. In this program, the M. rosenbergii resources were widely collected from four countries, the origin of the founders was verified with 16 microsatellites and the pedigree was reconstructed, and the optimum contribution selection was used to make the mating design. In this study, we evaluated the genetic parameters and selection response for the harvest body weight (HBW) of M. rosenbergii after being communally reared for 95-109 days. The data were collected from two generations that comprised 25,212 progenies from 150 sires and 198 dams. The residual maximum-likelihood methodology was employed to evaluate the variance components, by fitting an animal model. The accuracy of estimated breeding values increased by 0.38% after pedigree reconstruction using microsatellite markers. The estimated heritability (h2) for HBW was moderate (0.212 ± 0.049) and the common environmental coefficient (c2) was low (0.063 ± 0.017) when all the data were used for the analysis. Within generations, h2 was moderate to high (0.198 ± 0.080 to 0.338 ± 0.049). c2 could only be estimated in G1, which was 0.055 ± 0.030. The average HBW of males was significantly larger than that of females (P < 0.01). h2 estimated for female HBWs were higher than that for males within generations, while h2 estimated for female HBWs were lower than that for males across generations. But they were not significantly different (P > 0.05). The genetic correlations between sexes were moderate to high within each generation (0.529 to 0.763). Two methods were used to estimate the realized response. One method was calculated from the differences between the least squares means of the selected population HBW and that of control population HBW, which was 14.01%. The other method was calculated from the differences between the EBVs of the selected population HBW and that of control population HBW, which was 11.52%. The predicted responses derived from two sets of genetic parameters acquired from within- and across- generation datasets were 11.68% and 10.67%, respectively. The present study provides valuable information for breeding programs of M. rosenbergii., Competing Interests: Jiangsu Shufeng Prawn Breeding Co. was responsible for breeding prawns and data collection. This does not alter our adherence to PLOS ONE policies on data sharing and materials.

Genetic polymorphisms of folate pathway genes have been reported to be associated with congenital heart diseases (CHDs); however, the results remain conflicting. We conducted a family-based case-control study, which included160 CHD case-parent triads and 208 control-parent triads to explore the association of 18 genetic variants of seven folate metabolism-related genes with the risk of CHDs. The MTR C allele of rs1770449 (OR = 1.961, 95%CI: 1.379-2.788) and the MTR A allele of rs1050993 (OR = 1.994, 95%CI: 1.401-2.839) in infants were associated with an increased risk of CHDs. Over-transmission of SNPs rs1770449 and rs1050993 and haplotype CAA (rs1770449-rs1805087-rs1050993) in MTR were detected in total CHDs. The above mentioned associations of MTR with CHDs were also observed in septal defects and conotruncal heart defects subgroups. Without maternal periconceptional folate intake, the risk of CHDs among women carrying the rs1770449 "CT or CC" genotype or the rs1050993 "AG or AA" genotype in MTR was 3.262(95%CI: 1.656-6.429) or 3.263(95%CI: 1.656-6.429) times greater than the aOR in women carrying wild genotype, respectively. Our study suggests that MTR polymorphisms (rs1770449 and rs1050993) may be associated with the risk of CHDs and modify the relation between maternal folate intake and CHDs.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population., Methods: To evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets., Results: After adjusting for age and gender, the "AA" genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05-3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03-4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13-5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04-4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01-4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs., Conclusions: This study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.

Aim: A genomic region on 5q33.3 lies between and encompasses the IL12B and PTTG1 genes, and contains many potential psoriasis causal variants. We aimed to further examine the influence of variants in and around this region., Materials & Methods: We used least absolute shrinkage and selection operator (LASSO)-based regression analysis to assess independent contributions of 2171 variants to psoriasis susceptibility and tested them for association with different clinical psoriasis subtypes., Results: We found that ADRA1B gene variants contribute to psoriasis in Chinese population. ADRA1B gene variants have a stronger association with moderate-to-severe disease group and an earlier age at onset of psoriasis than IL-12B and PTTG1 variants., Conclusion: The association of variants in the ADRA1B gene with psoriasis could explain why variants in the IL-12B, ADRA1B and PTTG1 gene regions are associated with psoriasis.

Von Willebrand disease (VWD), the most common inherited bleeding disorder, is characterised by a variable bleeding tendency, heterogeneous laboratory phenotype and race specific distribution of mutations. The present study aimed to determine the correlation of genotype and phenotype in 200 Chinese individuals from 90 unrelated families with VWD. Next generation sequencing (NGS) of the whole coding VWF, copy number analysis of VWF by CNVplex ® technique as well as a comprehensive phenotypic assessment were carried out in all index patients (IPs). We identified putative mutations in all IPs except five mild type 1 (85/90, 94.4 %). In total, 98 different mutations were detected, 62 (63.3 %) of which were reported for the first time (23 missense mutations, 1 regulatory mutation, 12 splice site mutations and 26 null mutations). Mutations p.Ser1506Leu and p.Arg1374His/Cys/Ser were the most frequent mutations in 2A (33 % of cases) and 2M VWD (67 % of cases), respectively. In addition, mutation p.Arg816Trp was detected repeatedly in type 2N patients, while mutation p.Arg854Gln, extremely common in Caucasians, was not found in our cohort. Thirty-three patients had two or more putative mutations. Unlike most cases of type 1 and type 2 VWD, which were transmitted dominantly, we presented seven severe type 1, two type 2A and one type 2M with autosomal recessive inheritance. Here the phenotypic data of patients with novel mutations will certainly contribute to the better understanding of the molecular genetics of VWF-related phenotypes.

Accumulated evidence indicates that microRNA (miRNA or miR) is involved in the development of type 2 diabetes (T2DM). Several studies have shown that single nucleotide polymorphisms (SNPs) located in miRNAs are associated with T2DM in Caucasian populations. The association studies of miRNA's SNPs with T2DM in Asian are rarely reported, and there are distinct genetic differences between Caucasian and Asian populations. The focus of this study, therefore, is the association of T2DM with five SNPs (rs895819 in miR-27a, rs531564 in miR-124a, rs11888095 in miR-128a, rs3820455 in miR-194a and rs2910164 in miR-146a) located in five miRNAs in a Han Chinese population. A total of 738 subjects with T2DM and 610 non-diabetic subjects were genotyped using the TaqMan method. Next, the associations between the five SNPs with T2DM and individual metabolic traits were evaluated. Our data showed that the C allele of rs531564 in miR-124a may protect against T2DM (P=0.009, OR=0.758; 95%CI: 0.616-0.933). Conversely, the C allele of rs2910164 in miR-146a may increase the risk of developing T2DM (P<0.001, OR=1.459; 95%CI: 1.244-1.712). However, these five SNPs did not exhibit significant associations with individual metabolic traits in either the T2DM or non-diabetic groups. Our results revealed that genetic variations in miRNAs were associated with T2DM susceptibility in a Han Chinese population, and these results highlight the need to study the functional effects of these variants in miRNAs on the risk of developing T2DM.

Phaeochromocytomas (PCCs) and paragangliomas (PGLs) are rare, catecholamine-producing tumors. Most familial PCC/PGLs have been detected to be autosomal dominantly inherited. However, this study was undertaken in a family with PCCs to determine candidate genes in a dominant or recessive inheritance pattern. After excluding mutations in ten PCC/PGL susceptibility genes by Sanger sequencing, we used whole exome sequencing for screening on the four family members to discover novel candidate genes associated with PCCs. Based on the inexistence of non-synonymous mutations or indels in the ten known genes and the structure of this pedigree, 3 damaging loci with dominant inheritance pattern, and 5 damaging loci with recessive homozygous inheritance pattern and 6 damaging genes with compound heterozygous inheritance pattern were narrowed down to indicate the association with PCCs. According to the Gene Ontology (GO) category analysis on the combined results, cell adhesion showed the most significant enrichment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To investigate the relationship between child and adolescent obesity, and parental weight status., Methods: Height and weight were measured in Chinese children and adolescents aged 6-17 years old. Information was collected concerning parental weight and height, and possible covariates, using a questionnaire. The body mass index (BMI) of each study participant and their parents was calculated. On the basis of the BMI, parents were categorized as normal, overweight or obese, and children and adolescents were categorized as normal or obese., Results: Of the 5,041 participants included in the study, 6.82% were obese. Child or adolescent obesity was significantly associated with parental obesity. When both parents were obese, there was a 3.62-fold increased risk of obesity compared with those whose parents were of normal weight. Obesity in fathers was associated with a heightened risk of obesity in female children, whereas obesity in mothers was associated with a heightened risk of obesity in male children., Conclusions: Parental obesity was a predictor of obesity in children and adolescents. It is therefore of key importance to prevent obesity in children who have one or more obese parents.

Centromere mapping is an essential prerequisite for our understanding of the composition and structure of genomes. For centromere mapping, in two meiogynogenetic families of the Pacific abalone (Haliotis discus hannai), we screened 97 microsatellite markers that cover all linkage groups from a currently available abalone linkage map. Microsatellite analysis showed that no unique paternal allele was found in all gynogenetic progeny, which confirmed 100% success of induction of gynogenesis. In the control crosses, all 97 microsatellite loci were compatible with Mendelian inheritance, while in meiogynogenetic progeny, 5.2% of the microsatellite loci showed segregation distortions from an expected 1:1 ratio of two homozygote classes. The second division segregation frequency of the microsatellites ranged from 0.037 to 0.950 with a mean of 0.399, indicating the existence of interference. Heterogeneity among linkage groups in the crossover distribution was observed. Centromere location was mostly in accordance with the abalone karyotype, but differences in marker order between linkage and centromere maps occurred. Information on the positions of centromeres in relation to the microsatellite loci will represent a contribution towards assembly of genetic maps in the commercially important abalone species., (© 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.)

Objective: To investigate the polymorphisms of rs4906902 and rs8179184 loci in the promoter of the gamma-aminobutyric acid(GABA) receptor A, beta3 subunit gene (GABRB3), and their relevance with schizophrenia., Methods: PCR and DNA sequencing were used to detect the polymorphisms of rs4906902 and rs8179184 loci in 210 healthy individuals (control group) and 206 schizophrenic patients (case group) of the Han population in northern China. The chi2 test was used to identify Hardy-Weinberg equilibrium of the genotype distribution in the control group followed by comparing differences in genotype and haplotype frequency distributions between two groups., Results: Distributions of the genotype frequencies fit the law of Hardy-Weinberg equilibrium in the control group. rs4906902 and rs8179184 loci were in linkage disequilibrium and showed two haplotypes which were T-G and C-A. The differences of genotypic frequencies and haplotype frequencies were statistically significant between the two groups (P < 0.05). The frequency of haplotype C-A in the case group was significantly higher than in the control group. Genotypic and haplotype frequencies in the maternal line and paternal line were statistically significant in the case group (P < 0.05)., Conclusion: The haplotype of C-A in rs4906902 and rs8179184 loci in the promoter of GABRB3 gene may be maternally inherited and positively associated with schizophrenia and may be a useful tool in the forensic identification of schizophrenia.

Objective: To investigate the clinical and genetical characteristics of a Chinese family with an autosomal-dominant inherited high-frequency sensorineural hearing loss., Method: Pedigree was drawn after investigation. Fifeteen family members were checked up, and detailed audiological examination was performed., Result: The proband of the kindred had been diagnosed with senserineural hearing loss. A Chinese family SX-G087 with non-sysdromic hearing loss was ascertained. The inheritance pattern of this family is autosomal dominant based on the investigated information. The affected members showed postlingual, progressive, bilateral moderate to severe sensorineural hearing impairment. The age of onset varied from 20 to 35 years. The hearing loss began at high frequencies, and lower frequencies became involved with increasing age., Conclusion: Pedigree analysis suggested an autosomal-dominant inheritance pattern in this family. The information should facilitate linkage analysis and positional cloning for the causative gene of this family.

Objective: To determine the role of genetic and environmental factors in the onset of smoking in Chinese male twins., Methods: Retrospective data on initiation and age at onset of smoking, reported by 1,006 adult twin pairs [aged 18 year-old or more, 638 pairs of monozygotic (MZ) twins and 368 pairs of dizygotic (DZ) twins] were analyzed to calculate the heritability of smoking behavior and smoking initiation., Results: Different from western culture, 66.8% of males in this Chinese sample are smokers or have the experience of smoking, but only 0.2% of females do so. In the MZ twins, 88.7% (566/638 pairs) of them are both smokers or have smoking experience or both non-smokers, while the number is 63.6% (234/368 pairs) in the DZ twins. The heritability of smoking in this Chinese twin sample is 69.0%+/-4.1%. The smokers usually started their smoking at the age of 20.4+/-5.3 years old. The correlation coefficient for age at onset of smoking in male MZ twin smokers is 0.393, compared to correlation coefficient 0.860 in male DZ twin smokers., Conclusion: The moderate level of heritability shows that genetic factors have influence on smoking choice; when the smokers start their smoking, however, this depends more on individual environmental variation in our Chinese twin sample.

Objective: To study the level and heritability of serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) in adult twins sampled from Qingdao City of China., Methods: 316 pairs of healthy twin aged 18 to 60 years were recruited from the database of Qingdao City twin registry. Fasting serum lipids were detected by automatic biochemical analyzer. The zygosity of twins was established by using polymorphic DNA-based microsatellite markers. The heritability was estimated by formulating univariate ACE twin mode in Mx soft., Results: The average levels of fasting serum TC, HDL-C, LDL-C and TG were (4.52 +/- 1.08), (1.46 +/- 0.39), (2.58 +/- 0.79) and (1.11 +/- 0.77) mmol/L, respectively. The best fitting models adjusted by sex and age in Mx soft were AE model for TC, HDL-C and LDL-C, whereas CE model for TG. The heritability of TC, HDL-C, LDL-C and TG were 53% , 62% , 57% and 0, respectively., Conclusion: It is considered that both genetic and environmental factors may influence the level of TC, HDL-C and LDL-C, whereas environmental effect may be the factor essential for the level of TG.

Purpose: To investigate the distribution and heritability of iris thickness and pupil diameter measured by anterior segment optical coherence tomography (ASOCT) in a classic twin study., Methods: Twins aged 8 to 16 years were enrolled from the Guangzhou Twin Registry. ASOCT was used to obtain one horizontal scan, and the images were analyzed with custom software. Iris thickness was measured at 750 microm (IT750) and 2000 microm (IT2000) from the scleral spur, as well as cumulative iris area (IAREA). Pupil diameter in millimeters (PDMM) was measured between the most central points of the iris at the nasal and temporal sides. Zygosity was confirmed by genotyping in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling after adjustment for age and sex with the Mx program., Results: Participating in the analysis were 309 monozygotic (MZ) and 165 dizygotic (DZ) twin pairs. The mean IT750, IT2000, and IAREA were 0.406+/-0.075 (SD) mm, 0.514+/-0.075 mm, and 1.169+/-0.184 mm(2), whereas the PDMM was 5.600+/-0.0821 mm. The intraclass correlation coefficients for the IT750, IT2000, IAREA, and PDMM were 0.53, 0.54, 0.61, and 0.63 for MZ pairs and 0.29, 0.11, 0.35, and 0.34 for DZ pairs, respectively. A model with additive genetic and unique environmental effect was the most parsimonious, and the heritability was approximately 60% for iris thickness and pupil diameter., Conclusions: Iris thickness is thinner in girls but is not associated with age in children. The variation is largely attributable to additive genetic effects.

Objective: To investigate the epidemiological, genealogic characteristic, familial history of the families with fatal familial insomnia, its clinical and pathological features as well as the heredity rule of related genes., Methods: 135 familial members of 7 eras were studied. Vein blood samples from patients as well as from some familial members were collected. PRNP gene was studied with PCR, its serial was determined and then authenticated with Nsp I . Brain tissue was obtained for neuropathological test and PrP(Sc) test with Western blot method., Results: Clinical symptoms of the 2 diagnosed cases were typical. 11 familial members died of similar neural disease. 32 samples of their familial members, codon at D178N of PRNP of 11 members was mutated, with mutation rate as 34.38% while D129N showed as methionine. Brain tissue of both probands denaturalized into spongiform and the nerve fiber was absent but PrP(Sc) protein was identified., Conclusion: Genealogy was described in the family with fatal familial insomnia since the patients had typical clinical symptoms and pathological characteristics. It seemed necessary to confirm cases of fatal familial insomnia and their genealogy with epidemiological data and to investigate its gene characteristics as well as with neuropathological and Western blot tests.

The population dynamics, development of gonads, takeoff and flight behaviour of Aphis gossypii Glover were investigated in order to test whether there was variation of migratory ability in the spring population. Field surveys showed that not all the aphids overwintering on hibiscus migrated to the secondary host plants, and the host-alternating and host-specific life-cycle forms coexisted in Nanjing, China. Substantial variation in flight capacity of winged individuals, development of gonads and takeoff behaviour were found within the spring population. The frequency distribution of flight duration and the number of ovarioles per individual alatae exhibited two peaks, representing the migratory and sedentary genotypes, respectively. Significant response to directional selection on takeoff behaviour demonstrated the additive genetic component of this variation. Selection for 'takeoff' individuals caused a significant increase in takeoff angle from 39.8 degrees in the first selection to 68.7 degrees in the fifth; and, hence, screened out the migratory genotype (M), while selection for the sedentary individuals increased the rate of non-takeoffs significantly, and screened out the sedentary genotype (S). The reciprocal cross, M(female) x S(male), produced hybrid offspring performing significantly steeper takeoff angles compared with those from the cross S(female) x M(male), suggesting the presence of a maternal effect. On the other hand, takeoff rate was ranked as M(female) x S(male)=S(female) x M(male)>M>S, involving no sex-linkage and maternal effect. The coexistence of host-alternating and host-specific life-cycle forms of A. gossypii on the primary host has, as deduced from the present studies, a genetic basis.

Objective: To study the relationship between two common CBS gene variations, tHcy level and CHDs in a nuclear family-based study., Methods: 234 Chinese CHDs patients and their biological parents were recruited as case groups. And another 136 normal individuals and their parents were recruited as controls. The CBS gene 844ins68 and G919A variants were analyzed by PCR and PCR-ARMS methods. The serum fasting total homocysteine (tHcy) level was detected by Fluorescence Polarization Immunoassay., Results: CBS 844ins68 variant was associated with high risk of CHDs, the odds ratios (ORs) between heterozygotes (DI) versus wild homozygotes (DD) were 14.19 (95% CI: 2.21-591.52), 4.37 (95% CI: 1.24-23.47) and 4.77 (95% CI: 1.38-25.37) in mothers, fathers and offspring respectively (P < 0.05). CBS G919A was significantly associated with low risk of CHDs. The ORs of offspring between heterozygotes (GA) and mutant homozygotes (AA) versus wild homozygotes (GG) were 0.45 (95% CI: 0.23-0.87) and 0.34 (95% CI: 0.11-1.01), P < 0.05. And the parents carrying GA and AA genotypes also was lower risk of CHDs. For both of above two variants, the significant relations occurred especially in ventricular septal defect subgroup. Genotype combination analysis showed the more risk alleles (I and G) the family members carried, the higher the offspring risk of CHDs. And the serum fasting tHcy level was not significantly different among various groups and genotypes., Conclusion: CBS gene 844ins68 and G919A variations in nuclear families could be associated with CHDs risk of offspring, but not with serum fasting tHcy level.

Purpose: To estimate the heritability of the iridotrabecular angle width measured by anterior segment optical coherence tomography (ASOCT) in a classic twin study., Methods: Twins aged 8 to 16 years were identified from the Guangzhou Twin Registry. ASOCT was used to obtain one horizontal scan, and the images were analyzed with custom software. Angle width was represented by the angle opening distance (AOD) at the 500-microm anterior-to-scleral spur, as well as the angle recess area (ARA) and trabecular-iris space area (TISA) located 750 microm anterior to the scleral spur. Zygosity was confirmed by genotyping with 16 polymorphic markers in all same-sex twin pairs. Heritability was assessed by structural variance component genetic modeling after adjustment for age and sex, with the Mx program., Results: The mean age of the participants was 11.7 +/- 2.6 years in 305 monozygotic (MZ) and 11.8 +/- 2.4 years in 157 dizygotic (DZ) pairs. The intraclass correlation coefficients for the AOD, ARA, and TISA were 0.70, 0.75, and 0.72 in the MZ pairs and 0.34, 0.32, and 0.33 in the DZ pairs, respectively. A model with additive genetic (69.7%; 95% CI: 63.9%-74.6%) and unique environmental effects (30.3%; 95% CI: 25.4%-36.1%) was the most parsimonious for AOD. Similar results were identified for ARA and TISA., Conclusions: The variance in drainage angle width in Chinese children appears to be largely attributable to genetic effects, with a heritability of approximately 70%.

Purpose: To assess the heritability of disc area (DA), cup area (CA), and cup-disc area ratio (CDAR) as intermediate phenotypes for glaucoma in Chinese subjects in a classic twin study., Methods: Twins (n = 1160) aged 7 to 15 years were identified in the Guangzhou Twin Registry. Optic disc parameters were measured with a Heidelberg Retina Tomograph (HRT; Heidelberg Engineering GmbH, Heidelberg, Germany) by the same examiner and grader. Zygosity was confirmed by genotyping with 16 polymorphic markers in all same-sex twin pairs. The DA, CA, and CDAR of the right eyes were chosen as the traits of interest in the analysis. Heritability was assessed by structural variance component genetic modeling, with Mx quantitative genetic modeling software, after adjustment for age and gender., Results: Of those recruited, 1114 twins were identified in the analysis, including 355 monozygotic (MZ) and 202 dizygotic (DZ) twin pairs. The intraclass correlation coefficients were 0.79 for DA, 0.83 for CA, and 0.80 for CDAR in MZ pairs and 0.30, 0.37, and 0.35, respectively, in DZ pairs. The age- and sex-adjusted variance component model identified additive genetic and unshared environmental effects (AE model) being best fit for DA, CA, and CDAR. This best-fitting model yielded 77.3% additive genetic (95%CI: 73.0%-80.8%) and 22.7% unshared environment (95% CI: 19.2%-27.0%) for DA, 82.7% (95% CI:79.4%-85.5%) and 17.3% (95% CI: 14.5%-20.6%) for CA, 78.6% (95% CI: 74.5%-82.0%) and 21.4% (95% CI: 18.0%-25.4%) for CDAR., Conclusions: The variance of optic nerve head parameters (DA, CA, and CDAR) appears to be attributable to additive genetic and unshared environmental effects. Approximately 80% of these phenotypic variances are genetically determined.

Purpose: To assess the heritability of anterior chamber depth (ACD) and relative anterior chamber depth (ACD/axial length, rACD) in Chinese in a classic twin study., Methods: Twins aged 7 to 15 years living in two local districts were recruited from the Guangzhou Twin Registry. Anterior chamber depth and axial length were measured by partial coherence laser interferometry. Zygosity in all same-sex twin pairs was confirmed by genotyping with 16 polymorphic markers. The phenotypes of the right eyes were used in analysis. Heritability was assessed by structural variance component genetic modeling., Results: In total, 1126 twin participants were available for analysis, including 357 monozygotic (MZ) and 206 dizygotic (DZ) twin pairs. ACD increased with age (0.036 mm per year, P < 0.001) and 0.09 mm shallower in the girls than in the boys (P < 0.001). Age- and sex-adjusted intraclass correlation coefficients (ICCs) for ACD were 0.92 for the MZ and 0.50 for the DZ twins; those for rACD were 0.89 for the MZ and 0.52 for the DZ twins. The best-fitting model yielded 90.1% (95% CI: 88.2%-91.7%) of additive genetic and 9.9% (95% CI: 8.3%-11.8%) of unique environmental effects for ACD and 89.2% (95% CI: 87.1%-90.9%) of additive genetic and 10.8% (95% CI: 9.1%-12.9%) of unique environmental effects for rACD., Conclusions: Additive genetic effects appear to be the major contributor to the variation of ACD and rACD in Chinese population. High heritability remained even when the data were corrected for the influence of myopia.

Objective: To investigate the genetic mode of nasal polyp and the effect of genetic factor on occurrence of the disease., Methods: A genetic epidemiological case-control study including 280 pedigrees (120 nasal polyp cases and 160 controls) was conducted. The segregation ratio and the heritability of nasal polyp were respectively estimated by the Li-Mantel-Gart method and the Falconer method., Results: The segregation ratio was 0.124 (95% CI 0.081-0.167), significantly lower than 0.25, which showed that nasal polyp did not possess the characteristics of monogenetic model. The prevalence rate of first-degree and second-degree relatives in cases were 8.571% and 3.086% respectively, which were significantly different (X2 = 24.851, P < 0.01) and were higher than that noticed 1.376% and 1.141% in controls (X2 = 33.547 and 14.274, all P < 0.01). The heritability of the first-degree and second-degree relatives of nasal polyp was 64.488% and 61.947%. Among the first-degree relatives of nasal polyp probands, the heritability of the adult group and the children group were respectively 60.735% and 74.598% (the difference was significant, X2 = 4.504, P < 0.05). The heritability of the first-occurred group was 62.839% and the recurred group was 74.304% (the difference was significant, X2 = 4.105, P < 0.05)., Conclusions: This study indicated that the genetic model of nasal polyp belonged to polygenetic and the genetic factors played an important role in the occurrence of nasal polyp, especially for young or recurred patients.

Objective: To study the relationship between polymorphism of cystathionine beta synthase (CBS) gene and development of congenital heart disease (CHD)., Methods: One hundred and twenty-seven CHD case-parent triads were recruited from Liaoning Province as patient group, and 129 healthy subjects without family history of birth defect were simultaneously recruited as control group together with their biological parents. For all subjects the polymorphism of CBS gene G919A locus was examined by PCR-ARMS method., Results: The frequencies of three genotypes (w/w, w/m, and m/m) in control group were 27.2%, 58.4%, and 14.4%, respectively, with no significant difference in gender. A significant difference in the allele frequency was found between CHD patients and controls, the wild allele frequency was 67.9% in patients and 55.7% in controls. CHD parents' genotype distribution was significantly different from that in controls. Further comparison of each type of CHD showed that genotype frequencies in several CHD subtypes were significantly different from those in their corresponding controls. The results of TDT analysis showed that no allele transmission disequilibrium existed in CHD nuclear families., Conclusions: CBS gene G919A mutation is associated with the development of CHD, and the mutated allele may decrease the risk of CHD.

We report here on the characterization of a three-generation Chinese family with aminoglycoside-induced and nonsyndromic hearing impairment. Ten of 17 matrilineal relatives exhibited bilateral and sensorineural hearing impairment. Of these, nine matrilineal relatives, who had a history of exposure to aminoglycosides, exhibited variable severity and audiometric configuration of hearing loss. The dose and age at the time of drug administration seemed to be correlated with the severity of the hearing loss experienced by affected individuals. Sequence analysis of the complete mitochondrial genome in the pedigree showed the presence of homoplasmic A1555G mutation and 37 variants belonging to haplogroup D4a. Of those variants, the G7444A mutation is of special interest as the mutation at this position results in a read-through of the stop condon AGA of the COI message, thereby adding three amino acids (Lys-Gln-Lys) to the C-terminal of the polypeptide. Alternatively, the G7444A mutation is adjacent to the site of 3' end endonucleolytic processing of L-strand RNA precursor, spanning tRNA(Ser(UCN)) and ND6 mRNA. Thus, the G7444A mutation, similar to the deafness-associated A7445G mutation, may lead to a defect in the processing of the L-strand RNA precursor, thus influencing the phenotypic expression of the A1555G mutation. These data also imply that nuclear background plays a role in the aminoglycoside ototoxicity associated with the A1555G mutation in this Chinese pedigree., ((c) 2005 Wiley-Liss, Inc.)

Summary A pedigree of congenital stationary night blindness (CSNB) is described in a large Chinese family. The clinical description, pedigree, dark adaptation and elctroretinogram (ERG) studies indicate that the patients have an autosomal dominant form (ad) of CSNB. The disorder has been transmitted through at least 12 generations with over 40 affected individuals identified. The ERG data reveal that affected persons have severely diminished b-wave responses to dim light, but normal a-wave and subnormal b-wave responses to maximum light stimuli. The dark adaptation curves of three patients show a monophase curve, typical for night blindness. We have excluded the five previously known mutations in the three genes (RHO, PDE6B and GNAT1) associated with adCSNB, and linkage studies have excluded tight linkage between the disease locus and markers associated with these three genes. Thus, this family has adCSNB caused by a different gene from the previously identified RHO, PDE6B, and GNAT1.