A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?

@article{Ingram2006ANP,
  title={A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?},
  author={Catherine J. E. Ingram and Mohamed F. Elamin and Charlotte A. Mulcare and Michael E. Weale and Ayele Tarekegn and Tamiru Oljira Raga and Endashaw Bekele and Farouk M. Elamin and Mark George Thomas and Neil Bradman and Dallas M. Swallow},
  journal={Human Genetics},
  year={2006},
  volume={120},
  pages={779-788}
}
Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism (C-13910T) in an enhancer element 13.9 kb upstream of the lactase gene (LCT). The -13910*T allele occurs at very high frequency in northern Europeans as part of a very long haplotype (known as A), and promotes binding of the transcription factor Oct-1. However, -13910*T is at very low frequency in many African milk drinking pastoralist groups… 
Diversity of lactase persistence alleles in Ethiopia: signature of a soft selective sweep.
Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population
TLDR
The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil, which shows a high variability considering the number of L CT haplotypes observed.
The evolutionary genetics of lactase persistence in Africa and the Middle East
TLDR
The occurrence of only one -13910*T carrier out of 45 lactase persistent people from a cohort of phenotyped Sudanese individuals provided confirmation that the allele is not causal worldwide, and the cluster of lactase persistence associated alleles within a single regulatory element implies that they are causal.
The genetic variation of lactase persistence alleles in northeast Africa
TLDR
A 316bp region involved in regulating the expression of the LCT gene on chromosome 2 is sequenced, which encompasses five polymorphisms that have been associated with LP in Sudanese and South Sudanese populations, resulting in one of the greatest frequencies of LP-variants among all populations across the world.
Evolutionary and molecular genetics of regulatory alleles responsible for lactase persistence
TLDR
The results show that different mechanisms lead to a disruption of the normal down-regulation of lactase in adult life, and the finding of an extended region of high linkage disequilibrium in all populations, and an extended B haplotype is discussed in relation to the methods to study selection.
Screening for lactase persistence associated genotypes in cattle domestication groups of northern India
TLDR
Evaluated the frequency of C/T 13910 SNP among cattle domesticating groups of northern India and it was observed that frequency of LP phenotype and that of T 13910 allele of LP was much higher in these groups compared to those with no history of cattle domestication.
Ancient DNA Analysis Reveals High Frequency of European Lactase Persistence Allele (T-13910) in Medieval Central Europe
TLDR
DNA extracted from the dentine of 36 individuals excavated at a medieval cemetery in Dalheim, Germany suggests that genetic lactase persistence likely reached modern levels before the historic population declines associated with the Black Death, thus excluding plague-associated evolutionary forces in the rise of lactases persistence in this region.
Genetic origins of lactase persistence and the spread of pastoralism in Africa.
Population Genetics of Lactase Persistence and Lactose Intolerance
TLDR
The phenotypic polymorphism and the evidence that the genetic trait involves regulation of expression of the lactase gene and is caused by multiple independent mutations that have reached high frequencies in different populations, because of the benefits of drinking milk are described.
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References

SHOWING 1-10 OF 42 REFERENCES
Lactase haplotype frequencies in Caucasians: association with the lactase persistence/non‐persistence polymorphism
TLDR
It appears that lactase persistence arose more recently than the DNA marker polymorphisms used here to define the main Caucasian haplotypes, possibly as a single mutation on the A haplotype background.
An upstream polymorphism associated with lactase persistence has increased enhancer activity.
TLDR
The discovery of a functional difference between the 2 alleles at position -13910 supports the notion that the molecular difference between lactase persistence and nonpersistence is caused by the mutation at position-13910.
Identification of a variant associated with adult-type hypolactasia
TLDR
A DNA variant, C/T−13910, completely associates with biochemically verified lactase non-persistence in Finnish families and a sample set of 236 individuals from four different populations, indicating that it is very old.
Microsatellite variation and evolution of human lactase persistence
TLDR
This study shows that a limited number of microsatellite loci may provide sufficient resolution to reconstruct key aspects of the evolutionary history of lactase persistence, providing an alternative to approaches based on large numbers of SNPs.
Common polymorphism in a highly variable region upstream of the human lactase gene affects DNA-protein interactions
TLDR
Analysis of sequence in four primate species and comparison with the published pig sequence shows that the overall sequence of this highly variable human region is conserved in pigs as well as primates, and that it lies within a 1 kb region which has been shown to control lactase downregulation in pigs.
T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro.
TLDR
The data suggest that the binding of Oct-1 to the T-13,910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population.
Genetic signatures of strong recent positive selection at the lactase gene.
TLDR
It is estimated that strong selection occurred within the past 5,000-10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection the authors observe are among the strongest yet seen for any gene in the genome.
Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element.
TLDR
The DNA region of the C/T_(13910) lactase persistence/non-persistence variant functions in vitro as a cis element capable of enhancing differential transcriptional activation of the lactase promoter.
A genetic test which can be used to diagnose adult-type hypolactasia in children
TLDR
Genetic test of C/T-13910 polymorphism can be used as a first stage screening test for adult-type hypolactasia during childhood and was associated with very low lactase activity in the majority of children tested at 8 years of age and in every child older than 12 years ofAge.
Beja and Nilotes: nomadic pastoralist groups in the Sudan with opposite distributions of the adult lactase phenotypes.
TLDR
The Beja are the first nomadic desert population in North Africa in whom a high prevalence of lactase persistence has been demonstrated on a numerically sufficient sample, and fits into a converging gradient of lactose gene frequencies along the Nile Valley.
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