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Byline: Priyanka. Srivastava, Chakshu. Chaudhry, Anupriya. Kaur, Shubha. Phadke, Inusha. Panigrahi Background: Cytogenetic microarray (CMA) has brought a revolution in the field of cytogenetics by improving resolution by 500 times [...]

The identification of chromosome abnormalities is an essential part of diagnosis and treatment of genetic disorders such as chromosomal syndromes and many types of cancer. Modern cytogenetic imaging techniques have improved the study of chromosome aberrations but they are most often used as adjuncts to traditional G-banded karyotype analysis. Molecular cytogenetic techniques such as comparative genomic hybridization, multicolor fluorescence in situ hybridization, and spectral karyotyping (SKY) are able to detect chromosome copy number changes and complex structural aberrations in cancers, particularly in hematological malignancies and solid tumors. However, banded chromosome analysis is essential to distinguish between normal and abnormal chromosomes. Currently available cytogenetic imaging software is designed to classify only normal chromosomes. The identification of the banded regions involved in the abnormal chromosomes is done manually. In this paper, we propose an algorithm to automate the banding analysis of abnormal chromosomes by comparing the information obtained by SKY for precise identification of translocation break points. Our algorithm is based on the dynamic time warping method in order to overcome the problems due to the nonrigid nature of chromosomes. The method has been implemented and successfully applied to detect chromosome translocations, deletions, and duplications in cell lines derived from solid tumors. Index Terms--Chromosomes, dynamic time warping (DTW), translocation.

The yeast TEL1 and MEC1 genes (homologous to the mammalian ATM and ATR genes, respectively) serve partially redundant roles in the detection of DNA damage and in the regulation of telomere length. Haploid yeast tell mec1 strains were subcultured nonselectively for ~200 cell divisions. The subcultured strains had very high rates of chromosome aberrations: duplications, deletions, and translocations. The breakpoints of the rearranged chromosomes were within retrotransposons (Ty or &-repeats), and these chromosome aberrations nonrandomly involved chromosome III. In addition, we showed that strains with the hypomorphic mec1-21 allele often became disomic for chromosome VIII. This property of the mec1-21 strains is suppressed by a plasmid containing the DNA2 gene (located on chromosome VIII) that encodes an essential nuclease/helicase involved in DNA replication and DNA repair.

We describe a second-generation deficiency kit for Drosophila melanogaster composed of molecularly mapped deletions on an isogenic background, covering ~77% of the Release 5.1 genome. Using a previously reported collection of FRT-bearing P-element insertions, we have generated 655 new deletions and verified a set of 209 deletion-bearing fly stocks. In addition to deletions, we demonstrate how the P elements may also be used to generate a set of custom inversions and duplications, particularly useful for balancing difficult regions of the genome carrying haplo-insufficient loci. We describe a simple computational resource that facilitates selection of appropriate elements for generating custom deletions. Finally, we provide a computational resource that facilitates selection of other mapped FRT-bearing elements that, when combined with the DrosDel collection, can theoretically generate over half a million precisely mapped deletions.

This paper explores the meaning of higher risk status to women undergoing prenatal maternal screening for chromosomal anomalies. Quotations from lightly structured interviews and transcripts of pre-screening consultations in suburban London are used to illustrate pregnant women's diverse responses to the offer of screening, and to entering, living with and exiting from higher risk status. Some women reject screening in order to avoid the psychosocial and medical risks associated with higher risk status, or because they rule out pregnancy termination. They may question the risk selection implicitly built into the provision of preventative systems for some health problems but not others. Women who screen at higher risk may challenge this designation by questioning the system-specific probability used to separate them from the lower risk population. However, some experience distress even when they appreciate the precautionary basis on which their higher risk designation is based. They may find disengagement from higher risk status difficult after a diagnostic test has ruled out chromosomal anomalies. The findings highlight the complexity of communicating risk information to pregnant women and other screened populations, and emphasise the need to support those living with higher risk status and the benefits of keeping the time lived with this status as short as possible. Keywords: Chromosomal anomalies; Maternity care: Risk communication; Risk management; Prenatal screening; UK

Byline: Mirlene C.S.P. Cernach (1), Francy R.S. Patricio (2), Marcial F. Galera (3), Antonio F. Moron (4), Decio Brunoni (5) Keywords: autopsy; birth defects; congenital anomalies; genetic counseling; lethal anomalies; perinatal deaths Abstract: A study was conducted on 75 perinatal deaths with congenital anomalies through clinical, radiographic, cytogenetic, and autopsy evaluation, and the diagnoses of 72 patients (96%) were determined. In 11 patients with chromosomal anomalies, the cytogenetic study was sufficient to determine the diagnosis and the reproductive risk. In these cases, the value of the autopsy results resided above all in the description of the clinical variability. Radiographic evaluation was the best method to establish a diagnosis of skeletal dysplasias (14.7%). Furthermore, the X-rays showed small skeletal defects which are difficult to see on dissection. The clinical genetic evaluation with a detailed description of the phenotype and anthropometric exam, performed by a clinical geneticist, and the autopsy with gross and microscopic evaluation, facilitated the diagnoses of 50 cases (66.7%). We concluded that, in perinatal death with congenital anomalies, the teamwork of clinical geneticists and fetal pathologists increases the probability of determining the etiological diagnosis. This is essential to define the parents' reproductive risk, thus contributing to primary prevention of congenital anomalies. Author Affiliation: (1) Disciplina de Embriologia, Departamento de Morfologia, Universidade Federal de Sao Paulo--Escola Paulista de Medicina, Rua Botucatu, 740--Edificio Leitao da Cunha, 2deg andar, Sao Paulo--SP, Brazil sCEP--04023-900 (2) Setor de Patologia Pediatrica, Departamento de Anatomia Patologica, Universidade Federal de Sao Paulo--Escola Paulista de Medicina, Rua Botucatu, 740--Edificio Lemos Torres, 1deg andar, Sao Paulo--SP, Brazil CEP--04023-900 (3) Centro de Genetica Medica, Universidade Federal de Sao Paulo--Escola Paulista de Medicina, Rua Coronel Lisboa, 966--Vila Clementino, Sao Paulo--SP, Brazil CEP--04020-041 (4) Disciplina de Medicina Fetal, Departamento de Obstetricia, Universidade Federal de Sao Paulo--Escola Paulista de Medicina, Rua Napoleao de Barros, 715--8deg andar, Sao Paulo--SP, Brazil CEP--04024-002 (5) Disciplina de Genetica, Departamento de Morfologia, Universidade Federal de Sao Paulo--Escola Paulista de Medicina, Rua Botucatu, 740--Edificio Leitao da Cunha--1deg andar, Sao Paulo--SP, Brazil CEP--04023-900 Article History: Registration Date: 01/01/2001 Received Date: 05/11/2001 Accepted Date: 26/01/2004 Online Date: 17/06/2004

Researchers report the use of comparative genomic hybridization to analyze all of the chromosomes in a single human embryo before it was implanted during in vitro fertilization. In this case, the technique found no abnormal chromosomes and a healthy baby was born to a woman who had failed to get pregnant during several previous in vitro fertilization attempts.

Myeloid and lymphoblastic leukemias are characterized by translocations at 11q23, wherin breakpoints have been localized at gene MLL. The MLL gene was further characterized, resulting in the localization of a 9-kilobase region containing all the breakpoints of the translocation events. Subcloning of unique sequences within this region resulted in the development of DNA probes capable of detecting and characterizing DNA rearrangements in human leukemic cells with 11q23 translocations.

Prenatal diagnosis plays a very vital role in the diagnosis of various chromosome abnormalities and helps remove the fear of having a child with a severe mental or physical disability. However, such diagnosis brings along with it several moral and ethical as well as practical considerations, some of which are highlighted.

Cytochrome c oxidase (COX) is a complex enzyme structure that is critically important for oxidative respiration in the mitochondrion. The enzyme consists of 13 distinct subunits; the three largest, dubbed I, II, and III, constitute the actual enzymatic portion of the complex, while the other 10 participate in regulating the activity of the complex. Subunits I through III are coded for by DNA carried in the mitochondria themselves, while the remaining subunits are coded for by chromosomal DNA in the cell's nucleus. This enzyme complex is defective in a number of different syndromes of myopathy (muscle disease) and encephalomyopathy (neuromuscular disease). Two major forms of infantile myopathy involve abnormalities of cytochrome c oxidase and have completely opposite outcomes. One syndrome is invariably fatal and the other remits spontaneously during the first two or three years of life. When symptoms appear, it is difficult to distinguish between the fatal and benign forms of the deficiency. Biochemical studies do not easily make this differentiation, and more detailed biochemical studies might require more muscle biopsy material than would be appropriate to take from an infant. For this reason, an attempt was made to determine if immunohistochemical techniques could be used to distinguish between the fatal and benign forms of the disorder. Antibodies specific for different subunits of cytochrome c oxidase were used to stain histological sections of muscle biopsy material; considerably less of the precious biopsy material is required by this method. Muscle biopsies from four patients with fatal myopathy revealed a total lack of subunits VIIa and b, which are coded for by the nuclear DNA. This absence was observed in all muscle fibers. In contrast, the infants with benign myopathy lacked not only the subunits VIIa and b, but also subunit II as well. However, as recovery progressed for these patients, it was possible to show that the muscle fibers could be successfully stained for these subunits. These results suggest that the patients with the benign myopathy are lacking in some regulatory function, but are capable of manufacturing properly working enzyme complexes in their muscle fibers as they mature. (Consumer Summary produced by Reliance Medical Information, Inc.)

* This report describes a patient not suspected of having Klinefelter syndrome during life but diagnosed with it following postmortem examination using fluorescent in situ hybridization (FISH) for sex chromosomes and hormone serum analysis. A 49-year-old Japanese man had a history of nephrosis, heavy alcohol consumption, diabetes mellitus, and liver cirrhosis and had been undergoing dialysis for 10 years. He died of ruptured esophageal varices. Autopsy revealed hypogonadism, suggesting Klinefelter syndrome. This was confirmed by FISH, which showed a mosaic 46XY, 47XXY karyotype, and by serum analysis, which revealed high luteinizing hormone and follicle-stimulating hormone and low testosterone levels. Autopsy also revealed a nodular, bilateral, testicular Leydig cell hyperplasia. This report illustrates the value of postmortem laboratory investigations, particularly FISH for sex chromosomes and serum hormone analysis, for the demonstration of clinically uncertain or "occult" Klinefelter syndrome., Klinefelter syndrome is the most common chromosomal abnormality, with a predominantly 47, XXY karyotype and typical clinical findings of infertility, hypogonadism, reduced body hair, gynecomastia, tall stature, and increased gonadotropins [...]

Comparative genomic hybridization can be used to analyze a cell taken from a fertilized egg for the presence of chromosomal abnormalities. Only eggs that have normal chromosomes would be implanted during in vitro fertilization. This would eliminate the risk of multiple pregnancy and increase the rate of implantation.