For instance, in the absence of selection, the rate of molecular evolution and the level of standing genetic variation are directly governed by the rate of mutation. However, mutation is not a homogenous process that occurs at a constant rate among lineages or within genomes, and variation in the rate and pattern of germ line mutation are therefore key factors in many aspects of evolutionary and population genetics. Mutational events are likely to arise in all cells of an organism but only those originating in germ cells are transmitted to subsequent generations, and thus are relevant to evolution.

Mutations constitute the ultimate source of genetic novelty required for evolution by natural selection. Male-biased mutation has implications for important aspects of evolutionary biology such as mate choice in relation to mutation load, sexual selection and the maintenance of genetic diversity despite strong directional selection, the tendency for a disproportionate large role of the X (Z) chromosome in post-zygotic isolation, and the evolution of sex. Another life-history correlate is sexual selection: when there is intense sperm competition among males, increased sperm production will be associated with a larger number of mitotic cell divisions in spermatogenesis and hence an increase in α m. The male mutation bias is positively correlated with the relative excess of cell divisions in the male compared to the female germ line, as evidenced by a generation time effect: in mammals, α m is estimated at approximately 4–6 in primates, approximately 3 in carnivores and approximately 2 in small rodents. For instance, assuming that a neutral sequence is analysed, that rate heterogeneity owing to other factors is cancelled out by the investigation of many loci and that the effect of ancestral polymorphism is properly taken into account, the male-to-female mutation rate ratio, α m, can be solved from the observed difference in rate of X and Y chromosome divergence. The concept of male-biased mutation has been thoroughly analysed in recent years using an evolutionary approach, in which sequence divergence of autosomes and/or sex chromosomes are compared to allow inference about the relative contribution of mothers and fathers in the accumulation of mutations. Haldane was the first to connect this association of replication and mutation to the difference in the number of cell divisions in oogenesis (low) and spermatogenesis (usually high), and the resulting sex difference in the rate of mutation.

One facet of mutation rate variation is the propensity for genetic change to correlate with the number of germ cell divisions, reflecting the replication-dependent origin of many mutations. Gallbladder cancer (GBC) epidemiology gallbladder neoplasms genetic predisposition to disease molecular genetics.Mutation has traditionally been considered a random process, but this paradigm is challenged by recent evidence of divergence rate heterogeneity in different genomic regions. In addition, the current knowledge on environmental and genetic risk associations for gallbladder cancer and the need for additional large-scale genome wide association studies (GWAS) are discussed. This article provides a comprehensive overview of the current epidemiology and risk and protective factors associated with gallbladder cancer development. Though the overall global incidence of gallbladder cancer is low, there is marked geographic variation and ethnic communities in Asia as well as Native American populations in both North and South America are affected disproportionately. Consequently, gallbladder cancer is highly lethal. The early development of gallbladder cancer is usually asymptomatic and gallbladder cancer has a high propensity to metastatic dissemination, thus most patients are diagnosed at intermediate to advanced stages for which there is no curative treatment. Gallbladder cancer (GBC) is a form of hepatobiliary malignancy that develops from the mucosal lining of the gallbladder.

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