Long contiguous stretches of homozygosity in the human genome

Li, Ling Hui; Ho, Sheng Feng; Chen, Chien Hsiun; Chi, Chun‐Wei; Wong, Wan Ching; Li, Li Ying; Hung, Shuen Iu; Chung, Wen Hung; Pan, Wen Han; Lee, Ming Ta Michael; Tsai, Fuu Jen; Chang, Ching Fen; Wu, Jer Yuarn; Chen, Yuan Tsong

doi:10.1002/humu.20399

Cited by 104 publications

(121 citation statements)

References 31 publications

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“…The longest track identified in the 55 URO individuals was 52.57 Mb, which is much greater than the 27.32 and 17.91 Mb previously described by Li et al 21 and Gibson et al, 22 respectively. These long tracts of homozygosity were frequently observed in our cohort and are due to RC resulting from consanguineous marriages going back more than three generations.…”

Section: Identified Rohmentioning

confidence: 50%

Genome-wide inbreeding estimation within Lebanese communities using SNP arrays

et al. 2014

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Consanguineous marriages have been widely practiced in several global communities with varying rates depending on religion, culture, and geography. In consanguineous marriages, parents pass to their children autozygous segments known as homozygous by descent segments. In this study, single-nucleotide polymorphisms were analyzed in 165 unrelated Lebanese people from Greek Orthodox, Maronite, Shiite and Sunni communities. Runs of homozygosity, total inbreeding levels, remote consanguinity, and population admixture and structure were estimated. The inbreeding coefficient value was estimated to be 1.61% in offspring of unrelated parents over three generations and 8.33% in offspring of first cousins. From these values, remote consanguinity values, resulting from genetic drift or recurrent consanguineous unions, were estimated in offspring of unrelated and first-cousin parents to be 0.61 and 1.2%, respectively. This remote consanguinity value suggests that for any unrelated marriages in Lebanon, the mates could be related as third cousins or as second cousins once removed. Under the assumption that 25% of marriages occur between first cousins, the mean inbreeding value of 2.3% may explain the increased incidence of recessive disease in offspring. Our analysis reveals a common ancestral population in the four Lebanese communities we studied.

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Section: Identified Rohmentioning

confidence: 50%

Genome-wide inbreeding estimation within Lebanese communities using SNP arrays

et al. 2014

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“…Research on ROHs has started to gain impetus, as evidenced by the increasing number of publications after the first study by Gibson et al 12 reported the abundance of ROHs in the human genome of outbred populations. Further studies have investigated the population characteristics of ROHs in healthy individuals, [13][14][15] and also performed association analyses to identify ROHs that are associated with complex diseases and traits in a case-control study design. [16][17][18] To circumvent the limitations of the previous study by Díaz de Ståhl et al, 10 we conducted a study in a Swedish population by genotyping 100 individuals using the Affymetrix SNP Array 6.0 (Affymetrix, Santa Clara, CA, USA).…”

Section: Introductionmentioning

confidence: 99%

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

Teo

Naidoo

et al. 2011

J Hum Genet

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The abundance of copy number variants (CNVs) and regions of homozygosity (ROHs) have been well documented in previous studies. In addition, their roles in complex diseases and traits have since been increasingly appreciated. However, only a limited amount of CNV and ROH data is currently available for the Swedish population. We conducted a population-based study to detect and characterize CNVs and ROHs in 87 randomly selected healthy Swedish individuals using the Affymetrix SNP Array 6.0. More than 600 CNV loci were detected in the population using two different CNV-detection algorithms (PennCNV and Birdsuite). A total of 196 loci were consistently identified by both algorithms, suggesting their reliability. Numerous diseaseassociated and pharmacogenetics-related genes were found to be overlapping with common CNV loci such as CFHR1/R3, LCE3B/3C, UGT2B17 and GSTT1. Correlation analysis between copy number polymorphisms (CNPs) and genome-wide association studies-identified single-nucleotide polymorphisms also indicates the potential roles of several CNPs as causal variants for diseases and traits such as body mass index, Crohn's disease and multiple sclerosis. In addition, we also identified a total of 14 815 ROHs X500 kb or 2814 ROHs X1M in the Swedish individuals with an average of 170 and 32 regions detected per individual respectively. Approximately 141 Mb or 4.92% of the genome is homozygous in each individual of the Swedish population. This is the first population-based study to investigate the population characteristics of CNVs and ROHs in the Swedish population. This study found many CNV loci that warrant further investigation, and also highlighted the abundance and importance of investigating ROHs for their associations with complex diseases and traits.

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“…25 This assessment is somewhat contrasted by other studies that suggest that long homozygous segments are common in the human genome. [28][29][30] However, our results indicate that small homozygous segments around 1 Mb in length are quite common in both inbred and outbred individuals with genome-wide totals in excess of 40Mb per average individual (data not shown). This result agrees with previous estimates of total homozygosity based on the length of each segment.…”

Section: Discussionmentioning

confidence: 64%

Consanguinity in Centre d’Étude du Polymorphisme Humain (CEPH) pedigrees

et al. 2012

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A set of Centre d'É tude du Polymorphisme Humain (CEPH) cell lines serves as a large reference collection that has been widely used as a benchmark for allele frequencies in the analysis of genetic variants, to create linkage maps of the human genome, to study the genetics of gene expression, to provide samples to the HapMap and 1000 Genomes projects, and for a variety of other applications. An explicit feature of the CEPH collection is that these multigenerational families represent reference panels of known relatedness, consisting mostly of three-generation pedigrees with large sibships, two parents, and grandparents. We applied identity-by-state (IBS) and identity-by-descent (IBD) methods to high-density genotype data from 186 CEPH individuals in 13 families. We identified unexpected relatedness between nominally unrelated grandparents both within and between pedigrees. For one pair, the estimated Cotterman coefficient of relatedness k1 exceeded 0.2, consistent with one-eighth sharing (eg, first-cousins). Unexpectedly, significant IBD2 values were discovered in both second-degree and parent-child relationships. These were accompanied by regions of homozygosity in the offspring, which corresponded to blocks lacking IBS0 in purportedly unrelated parents, consistent with inbreeding. Our findings support and extend a 1999 report, based on the use of short tandem-repeat polymorphisms, that several CEPH families had regions of homozygosity consistent with autozygosity. We benchmarked our IBD approach (called kcoeff) against both RELPAIR and PREST software packages. Our findings may affect the interpretation of previous studies and the design of future studies that rely on the CEPH resource.

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Long contiguous stretches of homozygosity in the human genome

Cited by 104 publications

References 31 publications

Genome-wide inbreeding estimation within Lebanese communities using SNP arrays

Genome-wide inbreeding estimation within Lebanese communities using SNP arrays

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals

Consanguinity in Centre d’Étude du Polymorphisme Humain (CEPH) pedigrees

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