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| Prediction of deleterious human alleles |
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| Author(s): Sunyaev S, Ramensky V, Koch I, Lathe W, Kondrashov AS, Bork P |
| Source: HUMAN MOLECULAR GENETICS Volume: 10 Issue: 6 Pages: 591-597 Published: MAR 15 2001 |
| Times Cited: 339 References: 36 |
| Abstract: Single nucleotide polymorphisms (SNPs) constitute the bulk of human genetic variation, occurring with an average density of similar to1/1000 nucleotides of a genotype, SNPs are either neutral allelic variants or are under selection of various strengths, and the impact of SNPs on fitness remains unknown. Identification of SNPs affecting human phenotype, especially leading to risks of complex disorders, is one of the key problems of medical genetics. SNPs in protein-coding regions that cause amino acid variants (nonsynonymous cSNPs) are most likely to affect phenotypes. We have developed a straightforward and reliable method based on physical and comparative considerations that estimates the impact of an amino acid replacement on the three-dimensional structure and function of the protein, We estimate that similar to 20% of common human non-synonymous SNPs damage the protein. The average minor allele frequency of such SNPs in our data set was two times lower than that of benign non-synonymous SNPs, The average human genotype carries approximately 10(3) damaging nonsynonymous SNPs that together cause a substantial reduction in fitness. |
| Document Type: Article |
| Language: English |
| Reprint Address: Bork, P (reprint author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany |
Addresses:
1. European Mol Biol Lab, D-69117 Heidelberg, Germany
2. Max Delbruck Ctr Mol Med, D-13122 Berlin, Germany
3. VA Engelhardt Mol Biol Inst, Moscow 117984, Russia
4. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA |
| Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Genetics & Heredity |
| IDS Number: 412BH |
| ISSN: 0964-6906 |
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