Methods for genetic linkage analysis using trisomies.

E Feingold; N E Lamb; S L Sherman

Home/Archive/PubMed

PubMed · 7847384

Methods for genetic linkage analysis using trisomies.

E Feingold·N E Lamb·S L Sherman

View original source ↗Export metadata ↓

Abstract

Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of "susceptibility" alleles inherited from the nondisjoining parent give increased likelihood of having the trait. Our mapping method is similar to identity-by-descent-based mapping methods using affected relative pairs and also to methods for mapping recessive traits using inbred individuals by looking for markers with greater than expected homozygosity by descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected homozygosity in the chromosomes inherited from the nondisjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the trait gene, a confidence interval for that distance, and methods for computing power and sample sizes. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers and how to test candidate genes.

Explore related subjects

Chromosome Mapping Diploidy Genetic Linkage Genetic Markers Genotype Homozygote Humans Models, Genetic Statistics as Topic Trisomy Journal Article Research Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

E Feingold, N E Lamb, S L Sherman. 1995. Methods for genetic linkage analysis using trisomies.. https://pubmed.ncbi.nlm.nih.gov/7847384/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2026

Mitotic karyotyping and FISH mapping of the gender-specific locus indicate an advanced XY system in Hippophae rhamnoides.

Hippophae rhamnoides ssp. turkestanica, a subdioecious plant inhabiting the cold desert of the Indian Himalaya, has gained immense recognition for its nutritional and medicinal values. In recent years, the plant species has proven to be a suitable system to understand the evolution of dioecy. Despite its biological significance, the cytogenetics of this dioecious plant is unclear due to various conflicting accounts of its X-Y chromosome system, particularly the length of Y-chromosome. In this study, we resolved these ambiguities through comprehensive cytogenetic analyses across diverse western Himalayan populations. Using morphometric analysis and fluorescence in situ hybridization (FISH) with a gender-specific marker (HRMSSR), we confirmed homomorphic XX chromosomes in females and heteromorphic sex-chromosomes in males with a notably smaller Y-chromosome. The investigation also revealed a predominant somatic chromosome number of 2n = 24, although minor deviations (2n = 18, 20, 22) appeared at the seed level. These findings highlight an evolutionarily advanced sex-chromosome system. This first detailed cytogenetic investigation of Himalayan Seabuckthorn provides critical insights into the chromosomal architecture, laying a crucial foundation for future evolutionary, genomic, and conservation studies in the species.

Chromosome Mapping↗

PubMed2001

A novel homozygous deletion at chromosomal band 6q27 in an ovarian cancer cell line delineates the position of a putative tumor suppressor gene.

Chromosomal band 6q27 is believed to contain a tumor suppressor gene important in the development of several cancer types, including ovarian cancer. However, repeated efforts to identify a tumor suppressor gene in this region have been unsuccessful. Because homozygous deletions have been useful in the positional cloning of a number of tumor suppressor genes, we initiated a systematic search for such deletions in ovarian cancer cell lines using 6q microsatellite markers. One of the cell lines, OV167, was found to contain an 80 kb homozygous deletion encompassing marker D6S193 at 6q27 but excluding nearby marker D6S297. No known genes were present in the deleted region. Because the homozygous deletion might affect the expression of nearby genes, we analyzed the expression of the two closest known genes flanking the deletion, RNASE6PL and RSK-3. The expression of these genes were unaffected by the homozygous deletion, suggesting that the functional target of the deletion is located between these two genes. A search of the region against expressed sequence tag (EST) databases revealed that it contained four sets of expressed sequences. The first expressed sequences were derived from a LINE repetitive element and were considered unlikely to represent a tumor suppressor gene. The other expressed sequence tags identified did not show homology to known genes and are currently being investigated. This data may significantly reduce the magnitude of the search for the 6q tumor suppressor gene as it suggests a small area as a prime target for investigation.

Chromosome Mapping↗

PubMed2001

Coparalogy: physical and functional clusterings in the human genome.

Two rounds of large-scale duplications are thought to have occurred in early vertebrate ancestry; this is now known as the "2R hypothesis." They have led to the constitution of subfamilies of paralogous genes. Chromosomal regions that contain present-day paralogs (paralogous regions or paralogons) have been identified in mammals. We show that sets of paralogons (PGs) can be assembled in a tentative "human genome paralogy map" that includes all autosomes and X. A total of 14 PGs, containing more than 1600 genes, were assembled in this paralogy map. Genes that belong to the same PG are coparalogs. We show that identification of coparalogy can be used (i) to broaden data on gene mapping, (ii) to identify physical gene clusters that derive from early cis-duplications, and (iii) to speculate on coevolution and coregulation of genes sharing a common structure or function (functional clusters). Thus, coparalogy analyses should parallel phylogenetic analyses and can help draw hypotheses on gene and genome evolution.

Chromosome Mapping↗