Kenneth Kidd

Publications (4)88.23 Total impact

• Article: The molecular origin and consequences of escape from miRNA regulation by HLA-C alleles.

  Colm O'huigin, Smita Kulkarni, Yunping Xu, Zhihui Deng, Judith Kidd, Kenneth Kidd, Xiaojiang Gao, Mary Carrington
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  ABSTRACT: Differential expression of human leukocyte antigen C (HLA-C) allotypes is mediated by the binding of a microRNA, miR-148a, to the 3' untranslated region of some, but not all, HLA-C alleles. The binding results in lower levels of HLA-C expression, which is associated with higher levels of HIV-1 viral load among infected individuals. The alternative set of HLA-C alleles has several substitutions in the miR-148a binding site that prevent binding and HLA-C downregulation; these high-expression alleles associate with control of HIV-1 viral load. We show that the common ancestor of all extant HLA-C alleles was suppressed by miR-148a. Substitutions that prevent miR-148a binding arose by a sequence exchange event between an HLA-C allele and an HLA-B (MIM 142830) allele of a B(∗)07-like lineage. The event occurred 3-5 million years ago, resulting in an HLA-C variant that escape from miR-148a downregulation. We present evidence suggesting that selection played a role in the successful spread of the HLA-C escape alleles, giving rise to 7 of the 14 extant HLA-C lineages. Notably, critical peptide and KIR binding residues of the escape variants have selectively converged to resemble the sequence of their inhibited counterparts, such that the inhibited and escape groupings differ primarily by their levels of expression.
  The American Journal of Human Genetics 09/2011; 89(3):424-31. · 10.60 Impact Factor
• Source

  Available from: Manohar Furtado

  Article: SNPs for a universal individual identification panel.

  Andrew J Pakstis, William C Speed, Rixun Fang, Fiona C L Hyland, Manohar R Furtado, Judith R Kidd, Kenneth K Kidd
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  ABSTRACT: An efficient method to uniquely identify every individual would have value in quality control and sample tracking of large collections of cell lines or DNA as is now often the case with whole genome association studies. Such a method would also be useful in forensics. SNPs represent the best markers for such purposes. We have developed a globally applicable resource of 92 SNPs for individual identification (IISNPs) with extremely low probabilities of any two unrelated individuals from anywhere in the world having identical genotypes. The SNPs were identified by screening over 500 likely/candidate SNPs on samples of 44 populations representing the major regions of the world. All 92 IISNPs have an average heterozygosity [0.4 and the F(st) values are all\0.06 on our 44 populations making these a universally applicable panel irrespective of ethnicity or ancestry. No significant linkage disequilibrium (LD) occurs for all unique pairings of 86 of the 92 IISNPs (median LD = 0.011) in all of the 44 populations. The remaining 6 IISNPs show strong LD in most of the 44 populations for a small subset (7) of the unique pairings in which they occur due to close linkage. 45 of the 86 SNPs are spread across the 22 human autosomes and show very loose or no genetic linkage with each other. These 45 IISNPs constitute an excellent panel for individual identification including paternity testing with associated probabilities of individual genotypes less than 10(-15), smaller than achieved with the current panels of forensic markers. This panel also improves on an interim panel of 40 IISNPs previously identified using 40 population samples. The unlinked status of the subset of 45 SNPs we have identified also makes them useful for situations involving close biological relationships. Comparisons with random sets of SNPs illustrate the greater discriminating power, efficiency, and more universal applicability of this IISNP panel to populations around the world. The full set of 86 IISNPs that do not show LD can be used to provide even smaller genotype match probabilities in the range of 10(-31)-10(-35) based on the 44 population samples studied.
  Human Genetics 11/2009; 127(3):315-24. · 5.07 Impact Factor
• Article: Genetic variation in IL28B and spontaneous clearance of hepatitis C virus

  David L. Thomas, Chloe L. Thio, Maureen P. Martin, Ying Qi, Dongliang Ge, Colm O|[rsquo]|hUigin, Judith Kidd, Kenneth Kidd, Salim I. Khakoo, Graeme Alexander, James J. Goedert, Gregory D. Kirk, Sharyne M. Donfield, Hugo R. Rosen, Leslie H. Tobler, Michael P. Busch, John G. McHutchison, David B. Goldstein, Mary Carrington
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  ABSTRACT: Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide
  Nature 09/2009; 461(7265):798-801. · 36.28 Impact Factor
• Source

  Available from: Leslie H Tobler

  Article: Genetic variation in IL28B and spontaneous clearance of hepatitis C virus.

  David L Thomas, Chloe L Thio, Maureen P Martin, Ying Qi, Dongliang Ge, Colm O'Huigin, Judith Kidd, Kenneth Kidd, Salim I Khakoo, Graeme Alexander, James J Goedert, Gregory D Kirk, Sharyne M Donfield, Hugo R Rosen, Leslie H Tobler, Michael P Busch, John G McHutchison, David B Goldstein, Mary Carrington
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  ABSTRACT: Hepatitis C virus (HCV) infection is the most common blood-borne infection in the United States, with estimates of 4 million HCV-infected individuals in the United States and 170 million worldwide. Most (70-80%) HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma. Epidemiological, viral and host factors have been associated with the differences in HCV clearance or persistence, and studies have demonstrated that a strong host immune response against HCV favours viral clearance. Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the type III interferon IFN-3, was shown to associate strongly with more than a twofold difference in response to HCV drug treatment. To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (n = 388) or had persistent infection (n = 620). We show that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry. To our knowledge, this is the strongest and most significant genetic effect associated with natural clearance of HCV, and these results implicate a primary role for IL28B in resolution of HCV infection.
  Nature 09/2009; 461(7265):798-801. · 36.28 Impact Factor