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. 2010 Feb 9;10:36.
doi: 10.1186/1471-2148-10-36.

A Worldwide Correlation of Lactase Persistence Phenotype and Genotypes

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Free PMC article

A Worldwide Correlation of Lactase Persistence Phenotype and Genotypes

Yuval Itan et al. BMC Evol Biol. .
Free PMC article

Abstract

Background: The ability of adult humans to digest the milk sugar lactose - lactase persistence - is a dominant Mendelian trait that has been a subject of extensive genetic, medical and evolutionary research. Lactase persistence is common in people of European ancestry as well as some African, Middle Eastern and Southern Asian groups, but is rare or absent elsewhere in the world. The recent identification of independent nucleotide changes that are strongly associated with lactase persistence in different populations worldwide has led to the possibility of genetic tests for the trait. However, it is highly unlikely that all lactase persistence-associated variants are known. Using an extensive database of lactase persistence phenotype frequencies, together with information on how those data were collected and data on the frequencies of lactase persistence variants, we present a global summary of the extent to which current genetic knowledge can explain lactase persistence phenotype frequency.

Results: We used surface interpolation of Old World lactase persistence genotype and phenotype frequency estimates obtained from all available literature and perform a comparison between predicted and observed trait frequencies in continuous space. By accommodating additional data on sample numbers and known false negative and false positive rates for the various lactase persistence phenotype tests (blood glucose and breath hydrogen), we also apply a Monte Carlo method to estimate the probability that known lactase persistence-associated allele frequencies can explain observed trait frequencies in different regions.

Conclusion: Lactase persistence genotype data is currently insufficient to explain lactase persistence phenotype frequency in much of western and southern Africa, southeastern Europe, the Middle East and parts of central and southern Asia. We suggest that further studies of genetic variation in these regions should reveal additional nucleotide variants that are associated with lactase persistence.

Figures

Figure 1
Figure 1
Interpolated map of Old World LP phenotype frequencies. Dots represent collection locations. Colours and colour key show the frequencies of the LP phenotype estimated by surface interpolation.
Figure 2
Figure 2
Predicted Old World LP phenotype frequencies based on LP-associated allele frequencies. LP frequency prediction assumes Hardy-Weinberg equilibrium and dominance. Crosses represent collection locations where all 4 currently known LP-associated alleles were genotyped, and diamonds represent collection locations where the only data on the -13,910 C>T allele is available. Colour key shows the predicted LP phenotype frequencies estimated by surface interpolation.
Figure 3
Figure 3
Predicted Old World LP phenotype frequencies based on -13,910 C>T allele frequency data only. LP frequency prediction assumes Hardy-Weinberg equilibrium and dominance. Stars represent collection locations. Colour key shows the predicted LP phenotype frequencies estimated by surface interpolation.
Figure 4
Figure 4
Predicted Old World LP phenotype frequencies based on frequency data for the currently known LP associated allelic variants, excluding the -13,910 C>T allele. LP frequency prediction assumes Hardy-Weinberg equilibrium and dominance. Crosses represent collection locations. Colour key shows the predicted LP phenotype frequencies estimated by surface interpolation.
Figure 5
Figure 5
Old World LP genotype-phenotype correlation, obtained by calculating the quantitative difference between observed LP phenotype frequency and that predicted using frequency data on all 4 LP-associated alleles. Positive and negative values represent cases of LP-correlated genotype under- and over-predicting the LP phenotype, respectively. Dots represent LP phenotype collection locations, crosses represent data collection locations for all currently known 4 LP-correlated alleles, and diamonds represent -13,910 C>T only data collection locations. Colour key shows the values of the predicted LP phenotype frequencies (Figure 2) subtracted from the observed LP phenotype frequencies (Figure 1).
Figure 6
Figure 6
Old World LP genotype-phenotype correlation, obtained by the GenoPheno Monte Carlo test. Dots represent LP phenotype data collection locations, crosses represent data collection locations for all currently known 4 LP-correlated alleles, and diamonds represent collection locations for data on -13,910 C>T only. Colour key shows the p value obtained by the GenoPheno test. Red colour represents values of p < 0.01, indicating a highly significant lack of correlation, yellow colour represents values of 0.01 ≤ p < 0.05, indicating a significant lack of correlation, and blue colour represents values of p ≥ 0.05, indicating no significant lack of correlation.

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References

    1. Ingram CJ, Mulcare CA, Itan Y, Thomas MG, Swallow DM. Lactose digestion and the evolutionary genetics of lactase persistence. Hum Genet. 2009;124(6):579–591. doi: 10.1007/s00439-008-0593-6. - DOI - PubMed
    1. Heyman MB. Lactose intolerance in infants, children, and adolescents. Pediatrics. 2006;118(3):1279–1286. doi: 10.1542/peds.2006-1721. - DOI - PubMed
    1. Newcomer AD, McGill DB, Thomas PJ, Hofmann AF. Prospective comparison of indirect methods for detecting lactase deficiency. N Engl J Med. 1975;293(24):1232–1236. - PubMed
    1. Peuhkuri K. Lactose, lactase, and bowel disorders. Helsinki: University of Helsinki; 2000.
    1. Gudmand-Hoyer E, Skovbjerg H. Disaccharide digestion and maldigestion. Scand J Gastroenterol Suppl. 1996;216:111–121. doi: 10.3109/00365529609094566. - DOI - PubMed

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