Arnheim Norman, Calabrese Peter
Molecular and Computational Biology Program, University of Southern California, 1050 Childs Way, Los Angeles, California 90089-2910, USA.
Nat Rev Genet. 2009 Jul;10(7):478-88. doi: 10.1038/nrg2529.
Surprising findings about human germline mutation have come from applying new technologies to detect rare mutations in germline DNA, from analysing DNA sequence divergence between humans and closely related species, and from investigating human polymorphic variation. In this Review we discuss how these approaches affect our current understanding of the roles of sex, age, mutation hot spots, germline selection and genomic factors in determining human nucleotide substitution mutation patterns and frequencies. To enhance our understanding of mutation and disease, more extensive molecular data on the human germ line with regard to mutation origin, DNA repair, epigenetic status and the effect of newly arisen mutations on gamete development are needed.
关于人类生殖系突变的惊人发现来自于应用新技术检测生殖系DNA中的罕见突变、分析人类与近缘物种之间的DNA序列差异以及研究人类多态性变异。在本综述中，我们讨论了这些方法如何影响我们目前对性别、年龄、突变热点、生殖系选择和基因组因素在决定人类核苷酸替代突变模式和频率方面所起作用的理解。为了加强我们对突变和疾病的理解，需要更多关于人类生殖系的广泛分子数据，这些数据涉及突变起源、DNA修复、表观遗传状态以及新出现的突变对配子发育的影响。
