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Understanding what determines the frequency and pattern of human germline mutations Arnheim N; Calabrese PNat Rev Genet 2009[Jul]; 10 (7): 478-88Surprising 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.|*Epigenesis, Genetic[MESH]|*Germ Cells[MESH]|*Germ-Line Mutation[MESH]|*Mutation, Missense[MESH]|*Polymorphism, Genetic[MESH]|Aging[MESH]|DNA Mutational Analysis[MESH]|DNA Repair[MESH]|Female[MESH]|Humans[MESH]|Male[MESH]|Sex Characteristics[MESH] |
