For example, leptin with mutations on Ser-141 and Thr-142 totally lost its ability to activate leptin receptor but showed normal binding to leptin receptor [5].
Mutations in some Rho effectors are not lethal, for example animals with mutations in the DAG Kinase, dgk-1, which is negatively regulated by RHO-1, have defects in locomotion and egg laying [58] consistent with its function downstream of RHO-1.
For example, individuals with mutations in connexin, 30 present with nail dystrophy, some PPK and alopecia.
Portions of two example trees with mutations are shown at the top.
For example, patients with mutations in the BRCA1 or BRCA2 genes have a 36to85%5% chance of developing breast cancer compared with a 13% risk among the general female population [ 69, 70].
It is increasingly recognized that pharmacogenomics can play a key role in determining the susceptibility of the individual to the toxic effects of chemotherapy; for example, patients with mutations in the UGT1A1 gene have been found to be at increased risk of systemic toxicity from irinotecan.
In these cases a consistent fitness cost may appear if the resistant target displays a somewhat suboptimal functionality, as has been shown, for example, with some mutations in the gene rpsL conferring streptomycin in bacteria such as E. coli or Salmonella spp. [12].
Further studies of individuals, for example, with homozygous mutations in the vhl alleles with Chuvash polycythaemia may further clarify the importance of the HIF pathway in the pathogenesis of human disease in vivo.
For example, with the mutation densities of the hexaploid population (1 mutation per 38 kb), the probability of finding at least one an amino acid change in any 1.5 kb coding region is 2.5% ({1- [ 1-(1/38000)]}*0.66); as 66% of GC>AT codon changes are non-synonymous].
For example, CHH patients, with mutations in the RNA component of the ribonucleoprotein complex RNase MRP, present with disproportionate short stature and deficient cellular immunity [28], [37], reminiscent of the collagen X murine metaphyseal dysplasia and hematopoietic defects.
