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

Nabil Sabri Enattah; Tine G K Jensen; Mette Boyd; Rikke Lewinski; Mikko Kuokkanen; Heli Rasinpera; Hatem El-Shanti; Jeong Kee Seo; Michael Alifrangis; Insaf F Khalil; Abdrazak Natah; Ahmed Ali; Sirajedin Natah; David Comas; S Qasim Mehdi; Leif Groop; Else Marie Vestergaard; Faiqa Imtiaz; Mohamed S Rashed; Brian Meyer; Jesper Troelsen; Leena Peltonen

doi:10.1016/j.ajhg.2007.09.012

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

Nabil Sabri Enattah, Tine G K Jensen, Mette Boyd, Rikke Lewinski, Mikko Kuokkanen, Heli Rasinpera, Hatem El-Shanti, Jeong Kee Seo, Michael Alifrangis, Insaf F Khalil, Abdrazak Natah, Ahmed Ali, Sirajedin Natah, David Comas, S Qasim Mehdi, Leif Groop, Else Marie Vestergaard, Faiqa Imtiaz, Mohamed S Rashed, Brian MeyerJesper Troelsen, Leena Peltonen

213 Citations (Scopus)

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 allele: 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) approximately 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.

Original language	English
Journal	American Journal of Human Genetics
Volume	82
Issue number	1
Pages (from-to)	57-72
Number of pages	15
ISSN	0002-9297
DOIs	https://doi.org/10.1016/j.ajhg.2007.09.012
Publication status	Published - 2008

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10.1016/j.ajhg.2007.09.012

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Enattah, N. S., Jensen, T. G. K., Boyd, M., Lewinski, R., Kuokkanen, M., Rasinpera, H., El-Shanti, H., Seo, J. K., Alifrangis, M., Khalil, I. F., Natah, A., Ali, A., Natah, S., Comas, D., Mehdi, S. Q., Groop, L., Vestergaard, E. M., Imtiaz, F., Rashed, M. S., ... Peltonen, L. (2008). Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture. American Journal of Human Genetics, 82(1), 57-72. https://doi.org/10.1016/j.ajhg.2007.09.012

Enattah, NS, Jensen, TGK, Boyd, M, Lewinski, R, Kuokkanen, M, Rasinpera, H, El-Shanti, H, Seo, JK, Alifrangis, M, Khalil, IF, Natah, A, Ali, A, Natah, S, Comas, D, Mehdi, SQ, Groop, L, Vestergaard, EM, Imtiaz, F, Rashed, MS, Meyer, B, Troelsen, J & Peltonen, L 2008, 'Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture.', American Journal of Human Genetics, vol. 82, no. 1, pp. 57-72. https://doi.org/10.1016/j.ajhg.2007.09.012

@article{ef49cd4078e811dd81b0000ea68e967b,

title = "Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture.",

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 allele: 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) approximately 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 Mette Boyd and Rikke Lewinski and Mikko Kuokkanen and Heli Rasinpera and Hatem El-Shanti and Seo, {Jeong Kee} and Michael Alifrangis and Khalil, {Insaf F} and Abdrazak Natah and Ahmed Ali and Sirajedin Natah and David Comas and Mehdi, {S Qasim} and Leif Groop and Vestergaard, {Else Marie} and Faiqa Imtiaz and Rashed, {Mohamed S} and Brian Meyer and Jesper Troelsen and Leena Peltonen",

note = "Keywords: Alleles; Animals; Camels; Culture; Evolution, Molecular; Haplotypes; Humans; Lactase; Lactose Tolerance Test; Middle East; Milk; Polymorphism, Single Nucleotide; Saudi Arabia",

year = "2008",

doi = "10.1016/j.ajhg.2007.09.012",

language = "English",

volume = "82",

pages = "57--72",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "1",

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TY - JOUR

T1 - Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture.

AU - Enattah, Nabil Sabri

AU - Jensen, Tine G K

AU - Boyd, Mette

AU - Lewinski, Rikke

AU - Kuokkanen, Mikko

AU - Rasinpera, Heli

AU - El-Shanti, Hatem

AU - Seo, Jeong Kee

AU - Alifrangis, Michael

AU - Khalil, Insaf F

AU - Natah, Abdrazak

AU - Ali, Ahmed

AU - Natah, Sirajedin

AU - Comas, David

AU - Mehdi, S Qasim

AU - Groop, Leif

AU - Vestergaard, Else Marie

AU - Imtiaz, Faiqa

AU - Rashed, Mohamed S

AU - Meyer, Brian

AU - Troelsen, Jesper

AU - Peltonen, Leena

N1 - Keywords: Alleles; Animals; Camels; Culture; Evolution, Molecular; Haplotypes; Humans; Lactase; Lactose Tolerance Test; Middle East; Milk; Polymorphism, Single Nucleotide; Saudi Arabia

PY - 2008

Y1 - 2008

N2 - 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 allele: 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) approximately 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.

AB - 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 allele: 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) approximately 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.

U2 - 10.1016/j.ajhg.2007.09.012

DO - 10.1016/j.ajhg.2007.09.012

M3 - Journal article

C2 - 18179885

SN - 0002-9297

VL - 82

SP - 57

EP - 72

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 1

ER -

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

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