The population of the province of Newfoundland and Labrador (NL) has been a resource for genetic studies because of its historical isolation and increased prevalence of several monogenic disorders. Controversy remains regarding the genetic substructure and the extent of genetic homogeneity, which have implications for disease gene mapping. Population substructure has been reported from other isolated populations such as Iceland, Finland and Sardinia. We undertook this study to further our understanding of the genetic architecture of the NL population. We enrolled 494 individuals randomly selected from NL. Genome-wide SNP data were analyzed together with that from 14 other populations including HapMap3, Ireland, Britain and Native American samples from the Human Genome Diversity Project. Using multidimensional scaling and admixture analysis, we observed that the genetic structure of the NL population resembles that of the British population but can be divided into three clusters that correspond to religious/ethnic origins: Protestant English, Roman Catholic Irish and North American aboriginals. We observed reduced heterozygosity and an increased inbreeding coefficient (mean=0.005), which corresponds to that expected in the offspring of third-cousin marriages. We also found that the NL population has a significantly higher number of runs of homozygosity (ROH) and longer lengths of ROH segments. These results are consistent with our understanding of the population history and indicate that the NL population may be ideal for identifying recessive variants for complex diseases that affect populations of European origin.
Notes
Cites: Ann Med. 2009;41(3):234-4019160088
Cites: Clin Genet. 2002 Apr;61(4):233-4712030885
Cites: Clin Genet. 2013 Dec;84(6):522-3023278430
Cites: Nat Genet. 2000 Jul;25(3):320-310888882
Cites: Nat Genet. 2000 Jul;25(3):324-810888883
Cites: Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R167-7212915452
Cites: Nat Genet. 2006 May;38(5):556-6016582909
Cites: Nat Genet. 1999 Dec;23(4):397-40410581024
Cites: Am J Med Genet. 1988 Mar;29(3):649-603377008
Cites: Am J Hum Genet. 1999 Dec;65(6):1680-710577922