Is the most frequent allele the oldest?

Watterson, G. A.; Guess, Harry A.

doi:10.1016/0040-5809(77)90023-5

Cited by 245 publications

(151 citation statements)

References 7 publications

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“…Since population genetic theory suggests that the most frequent allele is the oldest (Watterson and Guess, 1977) and therefore likely to be the ancestral allele, we compared our data at the variable positions with the corresponding data from the chimpanzee reference sequence (http://www.genome.ucsc.edu/; March 2006 assembly). While the major allele at the majority (412 of 544; 76%) of variable sites in our data coincided with the ancestral (chimpanzee reference sequence) allele, at the remaining 132 (24%) sites the major allele is not the ancestral allele.…”

Section: Resultsmentioning

confidence: 99%

Genetic variation and haplotype structures of innate immunity genes in eastern India

Bairagya

Bhattacharya

et al. 2008

Infection, Genetics and Evolution

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This study reports results of an extensive and comprehensive study of genetic diversity in 12 genes of the innate immune system in a population of eastern India. Genomic variation was assayed in 171 individuals by resequencing ~75 kb of DNA comprising these genes in each individual. Almost half of the 548 DNA variants discovered was novel. DNA sequence comparisons with human and chimpanzee reference sequences revealed evolutionary features indicative of natural selection operating among individuals, who are residents of an area with a high load of microbial and other pathogens. Significant differences in allele and haplotype frequencies of the study population were observed with the HapMap populations. Gene and haplotype diversities were observed to be high. The genetic positioning of the study population among the HapMap populations based on data of the innate immunity genes substantially differed from what has been observed for Indian populations based on data of other genes. The reported range of variation in SNP density in the human genome is one SNP per 1.19 kb (chromosome 22) to one SNP per 2.18 kb (chromosome 19). The SNP density in innate immunity genes observed in this study (>3 SNPs kb −1 ) exceeds the highest density observed for any autosomal chromosome in the human genome. The extensive genomic variation and the distinct haplotype structure of innate immunity genes observed among individuals have possibly resulted from the impact of natural selection.

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Section: Resultsmentioning

confidence: 99%

Genetic variation and haplotype structures of innate immunity genes in eastern India

Bairagya

Bhattacharya

et al. 2008

Infection, Genetics and Evolution

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“…However, the assumption cannot be so easily swallowed that each lineage always traces in a much shorter time to a single ancestral haplotype within a restricted population of a single species that lacks an alternative population to provide ''infinitely many nonancestral chromosomes.'' The assumption that each lineage always traces in estimable time to a single ancestral haplotype (''most recent common ancestor'') that can be reliably inferred has other f laws: the rarest allele for each polymorphism in a haploset has a finite probability of being the oldest one, and so the probability that m polymorphisms all trace to a single ancestral haplotype tends to zero as m increases, and the most recent common ancestor and its associated time vary greatly along a chromosome (27).…”

Section: Discussionmentioning

confidence: 99%

A map of the human genome in linkage disequilibrium units

Tapper

Collins²,

Gibson³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Two genetic maps with additive distances contribute information about recombination patterns, recombinogenic sequences, and discovery of genes affecting a particular phenotype. Recombination is measured in morgans (w) over a single generation in a linkage map but may cover thousands of generations in a linkage disequilibrium (LD) map measured in LD units (LDU). We used a subset of single nucleotide polymorphisms from the HapMap Project to create a genome-wide map in LDU. Recombination accounts for 96.8% of the LDU variance in chromosome arms and 92.4% in their deciles. However, deeper analysis shows that LDU͞w, an estimate of the effective bottleneck time (t), is significantly variable among chromosome arms because (i) the linkage map is approximated from the Haldane function, then adjusted toward the Kosambi function that is more accurate but still exaggerates w for all chromosomes, especially shorter ones; (ii) the nonpseudoautosomal region of the X chromosome is subject to hemizygous selection; and (iii) at resolution less than Ϸ40,000 markers per w, there are indeterminacies (holes) in the LD map reflecting intervals of very high recombination. Selection and stochastic variation in small regions must have effects, which remain to be investigated by comparisons among populations. These considerations suggest an optimal strategy to eliminate holes quickly, greatly enhance the resolution of sex-specific linkage maps, and maximize the gain in association mapping by using LD maps.effective bottleneck time ͉ HapMap ͉ recombination ͉ interference ͉ selection A linkage map with 14,759 polymorphic markers has recently been published, far exceeding the density and coverage of earlier maps (1). Although the human genome sequence facilitated construction of this genetic map by determining the physical order of its markers, 56% of its intervals have recombination rates of zero. This observation demonstrates the relatively low resolution of the linkage map, for which a costly solution would be the analysis of many more pedigrees and markers. Alternatively, sperm typing offers recombination data of the highest resolution currently available (2) but is feasible only for very small regions in male chromosomes and does not reflect historical recombination events. Using the HapMap data (3) to construct linkage disequilibrium (LD) maps measured in LD units (LDU) (4) and interpolating them into the sex-specific linkage map enhances the resolution of the linkage map as a by-product of our main objective, which is to construct genomewide LD maps with additive LDU distances. Such maps are applicable to association mapping (5, 6), population comparisons (7-9), and identification of genomic regions that are influenced by selection (10). LD mapping has begun the task of explaining and exploiting complexities (8) that do not affect application of the Malecot model (4) to create an LD map but determine how the map should be used to increase resolution of the linkage map. LD Map Construction. LD maps were constructed by the methods in th...

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“…Since SNPs of lower minor-allele frequencies are in general those of younger age (Watterson and Guess 1977), applying minor-allele frequency cutoff is likened to eliminating recent SNPs of younger age. Though this may also risk losing some ancient SNPs with one of their alleles fixed in the population, Halushka et al (1999) found that only 5% of the rare SNPs that they investigated represent ancient allele that is being lost through evolution.…”

Section: Discussionmentioning

confidence: 99%

Inference from the relationships between linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related genes in four Asian populations

et al. 2004

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The extensive nucleotide diversity in drugrelated genes predisposes individuals to different drug responses and is a major problem in current clinical practice and drug development. Striking allelic frequency differences exist in these genes between populations. In this study, we genotyped 240 sites known to be polymorphic in the Japanese population in each of 270 unrelated healthy individuals comprising 90 each of Malaysian Malays, Indians, and Chinese. These sites are distributed in 109 genes that are drug related, such as genes encoding drug-metabolizing enzymes and drug transporters. Allele frequency and linkage disequilibrium distributions of these sites were determined and compared. They were also compared with similar data of 752 Japanese. Extensive similarities in allele frequency and linkage disequilibrium distributions were observed among Japanese, Malaysian Chinese, and Malays. However, significant differences were observed between Japanese and Malaysian Chinese with Malaysian Indians. These four populations were grouped into two genetic clusters of different ancestries. However, a higher correlation was found between Malaysian Malays and Indians, indicating the existence of extensive admixture between them. The results also imply the possible and rational use of existing single nucleotide polymorphism databases as references to assist future pharmacogenetic studies involving populations of similar ancestry.

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Is the most frequent allele the oldest?

Cited by 245 publications

References 7 publications

Genetic variation and haplotype structures of innate immunity genes in eastern India

Genetic variation and haplotype structures of innate immunity genes in eastern India

A map of the human genome in linkage disequilibrium units

Inference from the relationships between linkage disequilibrium and allele frequency distributions of 240 candidate SNPs in 109 drug-related genes in four Asian populations

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