TY - JOUR
T1 - Understanding the Hidden Complexity of Latin American Population Isolates
AU - Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes
AU - Mooney, Jazlyn A.
AU - Huber, Christian D.
AU - Service, Susan
AU - Sul, Jae Hoon
AU - Marsden, Clare D.
AU - Zhang, Zhongyang
AU - Sabatti, Chiara
AU - Ruiz-Linares, Andrés
AU - Bedoya, Gabriel
AU - Fears, Scott C.
AU - Service, Susan K.
AU - Kremeyer, Barbara
AU - Lic, Carmen Araya
AU - Lic, Xinia Araya
AU - Bejarano, Julio
AU - Lic, Margarita Ramirez
AU - Castrillón, Gabriel
AU - Lopez, Maria C.
AU - Montoya, Gabriel
AU - Montoya, Patricia
AU - Teshiba, Terri M.
AU - Altshuler, Lori
AU - Bartzokis, George
AU - Escobar, Javier
AU - Ospina-Duque, Jorge
AU - Risch, Neil
AU - Ruiz-Linares, Andrés
AU - Cantor, Rita M.
AU - Lopez-Jaramillo, Carlos
AU - Macaya, Gabriel
AU - Molina, Julio
AU - Reus, Victor I.
AU - Sabatti, Chiara
AU - Freimer, Nelson B.
AU - Bearden, Carrie E.
AU - Sul, Jae Hoon
AU - Huang, Alden Y.
AU - Ramensky, Vasily
AU - Hwang, Sun Goo
AU - Park, Young Jun
AU - Zhang, Zhongyang
AU - Olde Loohuis, Loes M.
AU - Spesny, Mitzi
AU - Gomez-Makhinson, Juliana
AU - Bedoya, Gabriel
AU - Coppola, Giovanni
AU - Freimer, Nelson
AU - Lohmueller, Kirk E.
N1 - Publisher Copyright:
© 2018 American Society of Human Genetics
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Most population isolates examined to date were founded from a single ancestral population. Consequently, there is limited knowledge about the demographic history of admixed population isolates. Here we investigate genomic diversity of recently admixed population isolates from Costa Rica and Colombia and compare their diversity to a benchmark population isolate, the Finnish. These Latin American isolates originated during the 16th century from admixture between a few hundred European males and Amerindian females, with a limited contribution from African founders. We examine whole-genome sequence data from 449 individuals, ascertained as families to build mutigenerational pedigrees, with a mean sequencing depth of coverage of approximately 36×. We find that Latin American isolates have increased genetic diversity relative to the Finnish. However, there is an increase in the amount of identity by descent (IBD) segments in the Latin American isolates relative to the Finnish. The increase in IBD segments is likely a consequence of a very recent and severe population bottleneck during the founding of the admixed population isolates. Furthermore, the proportion of the genome that falls within a long run of homozygosity (ROH) in Costa Rican and Colombian individuals is significantly greater than that in the Finnish, suggesting more recent consanguinity in the Latin American isolates relative to that seen in the Finnish. Lastly, we find that recent consanguinity increased the number of deleterious variants found in the homozygous state, which is relevant if deleterious variants are recessive. Our study suggests that there is no single genetic signature of a population isolate.
AB - Most population isolates examined to date were founded from a single ancestral population. Consequently, there is limited knowledge about the demographic history of admixed population isolates. Here we investigate genomic diversity of recently admixed population isolates from Costa Rica and Colombia and compare their diversity to a benchmark population isolate, the Finnish. These Latin American isolates originated during the 16th century from admixture between a few hundred European males and Amerindian females, with a limited contribution from African founders. We examine whole-genome sequence data from 449 individuals, ascertained as families to build mutigenerational pedigrees, with a mean sequencing depth of coverage of approximately 36×. We find that Latin American isolates have increased genetic diversity relative to the Finnish. However, there is an increase in the amount of identity by descent (IBD) segments in the Latin American isolates relative to the Finnish. The increase in IBD segments is likely a consequence of a very recent and severe population bottleneck during the founding of the admixed population isolates. Furthermore, the proportion of the genome that falls within a long run of homozygosity (ROH) in Costa Rican and Colombian individuals is significantly greater than that in the Finnish, suggesting more recent consanguinity in the Latin American isolates relative to that seen in the Finnish. Lastly, we find that recent consanguinity increased the number of deleterious variants found in the homozygous state, which is relevant if deleterious variants are recessive. Our study suggests that there is no single genetic signature of a population isolate.
KW - deleterious mutations
KW - identity by descent
KW - linkage disequilibrium
KW - pedigree
KW - population genetics
KW - population isolate
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U2 - 10.1016/j.ajhg.2018.09.013
DO - 10.1016/j.ajhg.2018.09.013
M3 - Article
C2 - 30401458
AN - SCOPUS:85056153122
SN - 0002-9297
VL - 103
SP - 707
EP - 726
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -