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

Abstract

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.

Pedigree-based estimation of human mobile element retrotransposition rates

“…The pedigrees were drawn from a population of primarily northern European descent which has experienced very low consanguinity (Jorde 1989), no evidence of founder effect (McLellan et al 1984), and heterozygosity similar to that of other populations of European ancestry (Xing et al 2009a). A previous study identified several related pairs of individuals in the Utah and non-Utah CEPH pedigrees (Stevens et al 2012), but only one mating pair used in our study had detectable consanguinity, with a coefficient of relationship of 0.001. Here, we present our findings of de novo L1, SVA, and Alu retrotransposition events in these pedigrees using three MEI-calling tools: MELT (Gardner et al 2017), RUFUS (https://github.com/ jandrewrfarrell/RUFUS) (Ostrander et al 2018), and TranSurVeyor (Rajaby and Sung 2018).…”

Analysis of 100 high-coverage genomes from a pedigreed captive baboon colony

“…The maxi-mum F ped was 0.40625 (n = 3). Thus, the degree of inbreeding within the colony is far greater than what has been observed in human populations (McQuillan et al 2008;Bittles and Black 2010;Stevens et al 2012).…”

Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population

“…IBD detection methods are useful in many contexts such as identifying phasing errors or polymorphic deletions, estimating heritability, 7 , 43 inferring kinship 4 , 38 , 44 , 45 , 46 and mapping diseases in association studies. 47 , 48 In cases, where genealogical information is not available we now know that IBD is an alternative to account for unknown relatedness.…”