人类基因发病率的生物信息学分析
Bioinformatical assay of human gene morbidity.
作者信息
Kondrashov Fyodor A, Ogurtsov Aleksey Y, Kondrashov Alexey S
机构信息
National Center for Biotechnology Information, National Institutes of Health, 38a Center Drive, 6S602, Bethesda, MD 20892, USA.
出版信息
Nucleic Acids Res. 2004 Mar 12;32(5):1731-7. doi: 10.1093/nar/gkh330. Print 2004.
Abstract
Only a fraction of eukaryotic genes affect the phenotype drastically. We compared 18 parameters in 1273 human morbid genes, known to cause diseases, and in the remaining 16 580 unambiguous human genes. Morbid genes evolve more slowly, have wider phylogenetic distributions, are more similar to essential genes of Drosophila melanogaster, code for longer proteins containing more alanine and glycine and less histidine, lysine and methionine, possess larger numbers of longer introns with more accurate splicing signals and have higher and broader expressions. These differences make it possible to classify as non-morbid 34% of human genes with unknown morbidity, when only 5% of known morbid genes are incorrectly classified as non-morbid. This classification can help to identify disease-causing genes among multiple candidates.
摘要
只有一小部分真核基因会对表型产生显著影响。我们比较了1273个已知会导致疾病的人类致病基因和其余16580个明确的人类基因中的18个参数。致病基因进化得更慢，系统发育分布更广，与黑腹果蝇的必需基因更相似，编码的蛋白质更长，含有更多的丙氨酸和甘氨酸，而组氨酸、赖氨酸和蛋氨酸较少，拥有更多数量的更长内含子，剪接信号更准确，并且具有更高和更广泛的表达。这些差异使得在未知发病情况的人类基因中，有34%可被归类为非致病基因，而只有5%的已知致病基因被错误地归类为非致病基因。这种分类有助于在多个候选基因中识别致病基因。
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1
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PLoS Biol. 2003 Nov;1(2):E45. doi: 10.1371/journal.pbio.0000045. Epub 2003 Nov 17.
2
An analysis of determinants of amino acids substitution rates in bacterial proteins.细菌蛋白质中氨基酸替代率的决定因素分析。
Mol Biol Evol. 2004 Jan;21(1):108-16. doi: 10.1093/molbev/msh004. Epub 2003 Oct 31.
3
Human disease genes: patterns and predictions.人类疾病基因：模式与预测
Gene. 2003 Oct 30;318:169-75. doi: 10.1016/s0378-1119(03)00772-8.
4
Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions.利用超敏rrf-3品系对线虫进行全基因组RNA干扰，揭示了新的基因功能。
PLoS Biol. 2003 Oct;1(1):E12. doi: 10.1371/journal.pbio.0000012. Epub 2003 Oct 13.
5
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Genome Res. 2003 Oct;13(10):2229-35. doi: 10.1101/gr.1589103.
6
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7
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