TY - JOUR
T1 - Herders of indian and european cattle share their predominant allele for lactase persistence
AU - Romero, Irene Gallego
AU - Mallick, Chandana Basu
AU - Liebert, Anke
AU - Crivellaro, Federica
AU - Chaubey, Gyaneshwer
AU - Itan, Yuval
AU - Metspalu, Mait
AU - Eaaswarkhanth, Muthukrishnan
AU - Pitchappan, Ramasamy
AU - Villems, Richard
AU - Reich, David
AU - Singh, Lalji
AU - Thangaraj, Kumarasamy
AU - Thomas, Mark G.
AU - Swallow, Dallas M.
AU - Lahr, Marta Mirazón
AU - Kivisild, Toomas
PY - 2012/1/1
Y1 - 2012/1/1
N2 - Milk consumption and lactose digestion after weaning are exclusively human traits made possible by the continued production of the enzyme lactase in adulthood. Multiple independent mutations in a 100-bp region-part of an enhancer-Approximately 14-kb upstream of the LCT gene are associated with this trait in Europeans and pastoralists from Saudi Arabia and Africa. However, a single mutation of purported western Eurasian origin accounts for much of observed lactase persistence outside Africa. Given the high levels of present-day milk consumption in India, together with archaeological and genetic evidence for the independent domestication of cattle in the Indus valley roughly 7,000 years ago, we sought to determine whether lactase persistence has evolved independently in the subcontinent. Here, we present the results of the first comprehensive survey of the LCT enhancer region in south Asia. Having genotyped 2,284 DNA samples from across the Indian subcontinent, we find that the previously described west Eurasian -13910 C>T mutation accounts for nearly all the genetic variation we observed in the 400- to 700-bp LCT regulatory region that we sequenced. Geography is a significant predictor of -13910*T allele frequency, and consistent with other genomic loci, its distribution in India follows a general northwest to southeast declining pattern, although frequencies among certain neighboring populations vary substantially. We confirm that the mutation is identical by descent to the European allele and is associated with the same >1 Mb extended haplotype in both populations.
AB - Milk consumption and lactose digestion after weaning are exclusively human traits made possible by the continued production of the enzyme lactase in adulthood. Multiple independent mutations in a 100-bp region-part of an enhancer-Approximately 14-kb upstream of the LCT gene are associated with this trait in Europeans and pastoralists from Saudi Arabia and Africa. However, a single mutation of purported western Eurasian origin accounts for much of observed lactase persistence outside Africa. Given the high levels of present-day milk consumption in India, together with archaeological and genetic evidence for the independent domestication of cattle in the Indus valley roughly 7,000 years ago, we sought to determine whether lactase persistence has evolved independently in the subcontinent. Here, we present the results of the first comprehensive survey of the LCT enhancer region in south Asia. Having genotyped 2,284 DNA samples from across the Indian subcontinent, we find that the previously described west Eurasian -13910 C>T mutation accounts for nearly all the genetic variation we observed in the 400- to 700-bp LCT regulatory region that we sequenced. Geography is a significant predictor of -13910*T allele frequency, and consistent with other genomic loci, its distribution in India follows a general northwest to southeast declining pattern, although frequencies among certain neighboring populations vary substantially. We confirm that the mutation is identical by descent to the European allele and is associated with the same >1 Mb extended haplotype in both populations.
KW - Haplotype
KW - India
KW - Lactase persistence
KW - Pastoralism
KW - Positive selection
UR - http://www.scopus.com/inward/record.url?scp=84856757955&partnerID=8YFLogxK
U2 - 10.1093/molbev/msr190
DO - 10.1093/molbev/msr190
M3 - Article
C2 - 21836184
AN - SCOPUS:84856757955
VL - 29
SP - 249
EP - 260
JO - Molecular Biology and Evolution
JF - Molecular Biology and Evolution
SN - 0737-4038
IS - 1
ER -