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Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture

Enattah, Nabil Sabri; Jensen, Tine G. K.; Nielsen, Mette; Lewinski, Rikke; Kuokkanen, Mikko; Rasinpera, Heli; El-Shanti, Hatem; Seo, Jeong Kee; Alifrangis, Michael and Khalil, Insaf F., et al. (2008) In American Journal of Human Genetics 82(1). p.57-72
Abstract
The T-13910 variant located in the enhancer element of the lactase (LCT) gene correlates perfectly with lactase persistence (LP) in Eurasian populations whereas the variant is almost nonexistent among Sub-Saharan African populations, showing high prevalence of LP. Here, we report identification of two new mutations among Saudis, also known for the high prevalence of LP. We confirmed the absence of the European T-13910 and established two new mutations found as a compound allete: T/G(-13915) within the -13910 enhancer region and a synonymous SNP in the exon 17 of the MCM6 gene T/C-3712, -3712 bp from the LCT gene. The compound allele is driven to a high prevalence among Middle East population(s). Our functional analyses in vitro showed that... (More)
The T-13910 variant located in the enhancer element of the lactase (LCT) gene correlates perfectly with lactase persistence (LP) in Eurasian populations whereas the variant is almost nonexistent among Sub-Saharan African populations, showing high prevalence of LP. Here, we report identification of two new mutations among Saudis, also known for the high prevalence of LP. We confirmed the absence of the European T-13910 and established two new mutations found as a compound allete: T/G(-13915) within the -13910 enhancer region and a synonymous SNP in the exon 17 of the MCM6 gene T/C-3712, -3712 bp from the LCT gene. The compound allele is driven to a high prevalence among Middle East population(s). Our functional analyses in vitro showed that both SNPs of the compound allele, located 10 kb apart, are required for the enhancer effect, most probably mediated through the binding of the hepatic nuclear factor 1 alpha (HNF1 alpha). High selection coefficient (s) similar to 0.04 for LP phenotype was found for both T-13910 and the compound allele. The European T-13910 and the earlier identified East African G(-13907) LP allele share the same ancestral background and most likely the same history, probably related to the same cattle domestication event. In contrast, the compound Arab allele shows a different, highly divergent ancestral haplotype, suggesting that these two major global LP alleles have arisen independently, the latter perhaps in response to camel milk consumption. These results support the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture. (Less)
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American Journal of Human Genetics
volume
82
issue
1
pages
57 - 72
publisher
Cell Press
external identifiers
  • wos:000253223800007
  • scopus:38749131273
ISSN
0002-9297
DOI
10.1016/j.ajhg.2007.09.012
language
English
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yes
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fe5f5812-d961-41f9-8b0c-e8ef3974c7c0 (old id 1197003)
date added to LUP
2008-09-10 13:51:48
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2017-10-08 03:27:02
@article{fe5f5812-d961-41f9-8b0c-e8ef3974c7c0,
  abstract     = {The T-13910 variant located in the enhancer element of the lactase (LCT) gene correlates perfectly with lactase persistence (LP) in Eurasian populations whereas the variant is almost nonexistent among Sub-Saharan African populations, showing high prevalence of LP. Here, we report identification of two new mutations among Saudis, also known for the high prevalence of LP. We confirmed the absence of the European T-13910 and established two new mutations found as a compound allete: T/G(-13915) within the -13910 enhancer region and a synonymous SNP in the exon 17 of the MCM6 gene T/C-3712, -3712 bp from the LCT gene. The compound allele is driven to a high prevalence among Middle East population(s). Our functional analyses in vitro showed that both SNPs of the compound allele, located 10 kb apart, are required for the enhancer effect, most probably mediated through the binding of the hepatic nuclear factor 1 alpha (HNF1 alpha). High selection coefficient (s) similar to 0.04 for LP phenotype was found for both T-13910 and the compound allele. The European T-13910 and the earlier identified East African G(-13907) LP allele share the same ancestral background and most likely the same history, probably related to the same cattle domestication event. In contrast, the compound Arab allele shows a different, highly divergent ancestral haplotype, suggesting that these two major global LP alleles have arisen independently, the latter perhaps in response to camel milk consumption. These results support the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture.},
  author       = {Enattah, Nabil Sabri and Jensen, Tine G. K. and Nielsen, Mette and Lewinski, Rikke and Kuokkanen, Mikko and Rasinpera, Heli and El-Shanti, Hatem and Seo, Jeong Kee and Alifrangis, Michael and Khalil, Insaf F. and Natah, Abdrazak and Ali, Ahmed and Natah, Sirajedin and Comas, David and Mehdi, S. Qasim and Groop, Leif and Vestergaard, Else Marie and Imtiaz, Faiqa and Rashed, Mohamed S. and Meyer, Brian and Troelsen, Jesper and Peltonen, Leena},
  issn         = {0002-9297},
  language     = {eng},
  number       = {1},
  pages        = {57--72},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2007.09.012},
  volume       = {82},
  year         = {2008},
}