Genetic adult lactase persistence is associated with risk of Crohn's Disease in a New Zealand population

Background: Mycobacterium avium subspecies paratuberculosis (MAP) is an infective agent found in ruminants and milk products, which has been suggested to increase the risk of gastrointestinal inflammation in genetically susceptible hosts. It is hypothesized that lactase persistence facilitates exposure to such milk products increasing the likelihood of adverse outcomes. Individuals either homozygous or heterozygous for the T allele of DNA variant, rs4988235, located 14kb upstream from the LCT locus, are associated with having lactase persistence. The aim of this study was to determine whether lactase persistence as evident by the T allele of rs4988235 is associated with Crohn's Disease (CD) in a New Zealand population. Findings: Individuals homozygous for the T allele (T/T genotype) showed a significantly increased risk of having CD as compared with those homozygous for the C allele (OR = 1.61, 95% CI = 1.03-2.51). Additionally, a significant increase in the frequency of the T allele was observed in CD patients (OR = 1.30, 95% CI = 1.05-1.61, p = 0.013), indicating that the T allele encoding lactase persistence was associated with an increased risk of CD. Conclusions: Our findings indicate that lactase persistence as evident by the presence of the T allele of rs4988235 is associated with risk of CD in this New Zealand Caucasian population

Evidence for Hitchhiking of Deleterious Mutations within the Human Genome

Deleterious mutations present a significant obstacle to adaptive evolution. Deleterious mutations can inhibit the spread of linked adaptive mutations through a population; conversely, adaptive substitutions can increase the frequency of linked deleterious mutations and even result in their fixation. To assess the impact of adaptive mutations on linked deleterious mutations, we examined the distribution of deleterious and neutral amino acid polymorphism in the human genome. Within genomic regions that show evidence of recent hitchhiking, we find fewer neutral but a similar number of deleterious SNPs compared to other genomic regions. The higher ratio of deleterious to neutral SNPs is consistent with simulated hitchhiking events and implies that positive selection eliminates some deleterious alleles and increases the frequency of others. The distribution of disease-associated alleles is also altered in hitchhiking regions. Disease alleles within hitchhiking regions have been associated with auto-immune disorders, metabolic diseases, cancers, and mental disorders. Our results suggest that positive selection has had a significant impact on deleterious polymorphism and may be partly responsible for the high frequency of certain human disease alleles

Mapping of HNF4α target genes in intestinal epithelial cells

© 2009 Boyd et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens