|Title||Haplotype and linkage disequilibrium architecture for human cancer-associated genes.|
|Publication Type||Journal Article|
|Year of Publication||2002|
|Authors||Bonnen, PE, Wang, PJ, Kimmel, M, Chakraborty, R, Nelson, DL|
|Date Published||2002 Dec|
|Keywords||Alleles, Cell Line, Transformed, Chromosome Mapping, Gene Frequency, Genes, Neoplasm, Genetic Markers, Genetic Predisposition to Disease, Genome, Human, Haplotypes, Humans, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Recombination, Genetic|
To facilitate association-based linkage studies we have studied the linkage disequilibrium (LD) and haplotype architecture around five genes of interest for cancer risk: ATM, BRCA1, BRCA2, RAD51, and TP53. Single nucleotide polymorphisms (SNPs) were identified and used to construct haplotypes that span 93-200 kb per locus with an average SNP density of 12 kb. These markers were genotyped in four ethnically defined populations that contained 48 each of African Americans, Asian Americans, Hispanic Americans, and European Americans. Haplotypes were inferred using an expectation maximization (EM) algorithm, and the data were analyzed using D', R(2), Fisher's exact P-values, and the four-gamete test for recombination. LD levels varied widely between loci from continuously high LD across 200 kb to a virtual absence of LD across a similar length of genome. LD structure also varied at each gene and between populations studied. This variation indicates that the success of linkage-based studies will require a precise description of LD at each locus and in each population to be studied. One striking consistency between genes was that at each locus a modest number of haplotypes present in each population accounted for a high fraction of the total number of chromosomes. We conclude that each locus has its own genomic profile with regard to LD, and despite this there is the widespread trend of relatively low haplotype diversity. As a result, a low marker density should be adequate to identify haplotypes that represent the common variation at a locus, thereby decreasing costs and increasing efficacy of association studies.
|Alternate Journal||Genome Res|
|PubMed Central ID||PMC187564|
|Grant List||R01 CA075432 / CA / NCI NIH HHS / United States |
CA75432 / CA / NCI NIH HHS / United States
Haplotype and linkage disequilibrium architecture for human cancer-associated genes.
|Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality. Nat Commun. 2023;14(1):6113..|
|PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects. Am J Hum Genet. 2023;110(10):1787-1803..|
|Chimeric RNAs reveal putative neoantigen peptides for developing tumor vaccines for breast cancer. Front Immunol. 2023;14:1188831..|