Constructing an initial map of transmission distortion based on high density HapMap SNPs across the human autosomes

Libin Deng^{a, b},
Dake Zhang^{b, c},
Elliott Richards^d,
Xiaoli Tang^a,
Jin Fang^e,
Fei Long^e,
Yan Wang^{e
, ,}

a.
Faculty of Basic Medical Science, Nanchang University, Nanchang 330006, China
b.
Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China
c.
Graduate School of Chinese Academy of Sciences, Beijing 100049, China
d.
Department of Biology, College of Life Sciences, Brigham Young University, Provo UT 84602, USA
e.
The Laboratory Center of Medicine, Nanchang University, Nanchang 330006, China

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Corresponding author: E-mail address: wyjxmc@sina.com (Yan Wang)

摘要

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Abstract: Transmission distortion (TD) is a significant departure from Mendelian predictions of genes or chromosomes to offspring. While many biological processes have been implicated, there is still much to be understood about TD in humans. Here we present our findings from a genome-wide scan for evidence of TD using haplotype data of 60 trio families from the International HapMap Project. Fisher's exact test was applied to assess the extent of TD in 629,958 SNPs across the autosomes. Based on the empirical distribution of and further permutation tests, we identified 1,205 outlier loci and 224 candidate genes with TD. Using the PANTHER gene ontology database, we found 19 categories of biological processes with an enrichment of candidate genes. In particular, the “protein phosphorylation” category contained the largest number of candidates in both HapMap samples. Further analysis uncovered an intriguing non-synonymous change in PPP1R12B, a gene related to protein phosphorylation, which appears to influence the allele transmission from male parents in the YRI (Yoruba from Ibadan, Nigeria) population. Our findings also indicate an ethnicity-related property of TD signatures in HapMap samples and provide new clues for our understanding of TD in humans.
- transmission distortion /
- HapMap Project /
- gene ontology

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参考文献(22)

[1]	Akey, J.M., Zhang, G., Zhang, K. et al. Interrogating a high-density SNP map for signatures of natural selection Genome Res., 12 (2002),pp. 1805-1814
[2]	Balding, D.J. A tutorial on statistical methods for population association studies Nat. Rev. Genet., 7 (2006),pp. 781-791
[3]	Becker, T., Knapp, M. A powerful strategy to account for multiple testing in the context of haplotype analysis Am. J. Hum. Genet., 75 (2004),pp. 561-570
[4]	Buffone, M.G., Doncel, G.F., Marin Briggiler, C.I. et al. Human sperm subpopulations: Relationship between functional quality and protein tyrosine phosphorylation Hum. Reprod., 19 (2004),pp. 139-146
[5]	Chakrabarti, R., Cheng, L., Puri, P. et al. Protein phosphatase PP1 gamma 2 in sperm morphogenesis and epididymal initiation of sperm motility Asian J. Androl., 9 (2007),pp. 445-452
[6]	Deng, L., Tang, X., Kang, J. et al. Scanning for signatures of geographically restricted selection based on population genomics analysis Chinese Sci. Bull., 52 (2007),pp. 2649-2656
[7]	Evans, D.M., Morris, A.P., Cardon, L.R. et al. Behav. Genet., 36 (2006),pp. 947-950
[8]	Hinds, D.A., Stuve, L.L., Nilsen, G.B. et al. Whole-genome patterns of common DNA variation in three human populations Science, 307 (2005),pp. 1072-1079
[9]	Hunter, T. Cooperation between oncogenes Cell, 64 (1991),pp. 249-270
[10]	Kelley, J.L., Madeoy, J., Calhoun, J.C. et al. Genomic signatures of positive selection in humans and the limits of outlier approaches Genome Res., 16 (2006),pp. 980-989
[11]	Maglott, D., Ostell, J., Pruitt, K.D. et al. Entrez Gene: Gene-centered information at NCBI Nucleic Acids Res., 35 (2007),pp. D26-D31
[12]	Pardo-Manuel de Villena, F., Sapienza, C. Nonrandom segregation during meiosis: The unfairness of females Mamm. Genome, 12 (2001),pp. 331-339
[13]	Pardo-Manuel de Villena, F., de la Casa-Esperon, E., Sapienza, C. Natural selection and the function of genome imprinting: Beyond the silenced minority Trends Genet., 16 (2000),pp. 573-579
[14]	Ryu, G.M., Song, P., Kim, K.W. et al. Genome-wide analysis to predict protein sequence variations that change phosphorylation sites or their corresponding kinases Nucleic Acids Res., 37 (2009),pp. 1297-1307
[15]	Santos, P.S., Hohne, J., Schlattmann, P. et al. Assessment of transmission distortion on chromosome 6p in healthy individuals using tagSNPs Eur. J. Hum. Genet., 17 (2009),pp. 1182-1189
[16]	Shi, M., Umbach, D.M., Weinberg, C.R. Identification of risk-related haplotypes with the use of multiple SNPs from nuclear families Am. J. Hum. Genet., 81 (2007),pp. 53-66
[17]	Steemers, F.J., Gunderson, K.L. Whole genome genotyping technologies on the BeadArray platform Biotechnol. J., 2 (2007),pp. 41-49
[18]	Su, A.I., Wiltshire, T., Batalov, S. et al. A gene atlas of the mouse and human protein-encoding transcriptomes Proc. Natl. Acad. Sci. USA, 101 (2004),pp. 6062-6067
[19]	The International HapMap Consortium A haplotype map of the human genome Nature, 437 (2005),pp. 1299-1320
[20]	Thomas, P.D., Kejariwal, A., Campbell, M.J. et al. PANTHER: A browsable database of gene products organized by biological function, using curated protein family and subfamily classification Nucleic Acids Res., 31 (2003),pp. 334-341
[21]	Visconti, P.E., Kopf, G.S. Regulation of protein phosphorylation during sperm capacitation Biol. Reprod., 59 (1998),pp. 1-6
[22]	Zöllner, S., Wen, X., Hanchard, N.A. et al. Evidence for extensive transmission distortion in the human genome Am. J. Hum. Genet., 74 (2004),pp. 62-72