title: Ethnic divergence and linkage disequilibrium of novel SNPs in the human NLI-IF gene: evidence of human origin and lack of association with tuberculosis susceptibility.
abstract: Sequence variation in the human genome has been used as a tool in studying human diseases and the evolutionary history of man. A human inherited predisposition to tuberculosis has been suggested and studied; however. genetic mechanisms are still ambiguous. In the present study, we scanned the regulatory and coding region of Nuclear LIM Interactor-Interacting Factor gene (NLI-IF), which is physically close to the tuberculosis-associated gene NRAMP1. Thirteen biallelic single-nucleotide polymorphisms (SNPs) were identified from four ethnic populations (African-American, Caucasian, Hispanic, and Asian) with population-specific distribution of alleles. The extent of linkage disequilibrium (LD) between 402T > C, and 472-42G > A varied distinctly from complete LD in the non-African-American groups to strong but incomplete LD in African-Americans. Both SNPs were in significant LD with the polymorphism 3' UTR in NRAMP1 among these ethnic groups (P < 0.02), except 402T > C in African-Americans. In a case-control study with a Caucasian population, three cosmopolitan SNPs (204C > A, 402T > C and 472 - 42G > A) in NLI-IF showed no significant association with human susceptibility to tuberculosis. Our results support the "out-of-Africa" model of human origin, and suggest the time for the common ancestor dispersing from Africa could not have been more than approximately 385,620 years ago.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: Shujun
authors.initials: S
authors.lastname: Dou
authors.forename: Paul
authors.initials: P
authors.lastname: Olsen
authors.forename: Larry
authors.initials: L
authors.lastname: Teeter
authors.forename: Gerald
authors.initials: G
authors.lastname: Adams
authors.forename: Edward
authors.initials: E
authors.lastname: Graviss
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010749:Phosphoprotein Phosphatases; D020641:Polymorphism, Single Nucleotide; D013781:Texas; D014376:Tuberculosis / Q000208:ethnology / Q000235:genetics*; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D009687:Nuclear Proteins; C413483:CTDSP1 protein, human; D010749:Phosphoprotein Phosphatases