Allowing free access to the bulk of the mutation data present in HGMD, while generating sufficient income from its commercial distribution to support its maintenance and expansion, represents a business model that should maximize the availability of HGMD at the same time as ensuring its long-term sustainability.
Compared to the distribution of mutation data present in the Universal VHL Mutation database with 747 mutations [ 31], the relative amount of point mutations is much higher in the database (64%), compared to the percentage of point mutations we observed (44%), as well as the frequency of nonsense mutations (11% vs. 3%).
Mutation data presented here will be useful for designing new DNA testing strategies for CF in South Brazil.
The disease-associated mutation data presented (Table 1, Table 2, Table 3) show a considerable proportion of novel disease genes as well as novel genetic variants within the Omani population.
With this program, users have the option of exploring mutation data (at present, only SNVs can be analyzed) linked to the original literature citations.
Summarising mutation data from the present study and previously published ones, it appears that cancers harbouring K- ras mutations represent a small fraction of the sinonasal adenocarcinomas.
As an example of the ability of a natural genetic variant to modify the effect of an engineered mutation, data will be presented that demonstrate that the effect of Chrna5 deletion on oral nicotine intake is dependent upon naturally occurring variant alleles of Chrna4.
Remaining mutations were compared with data present in the public databases dbSNP [ 10], COSMIC [ 11], and cBIO [ 12] to search for known pathogenic mutations.
Finally, an analysis among the seven animal species with the greatest number of published causal mutations (dog, cattle, cat, sheep, pig, horse and chicken) indicates homogeneity in the ratio of missense to non-sense mutations (data are presented in the last two rows of Table 1; χ = 11.76; df = 6; P = 0.07).
Greenman and colleagues [ 13] described methods to determine whether driver mutations are present in a mutation data set, to determine how many there are likely to be, and finally to give an indication of which genes they are likely to be in.
Because studies of chromosome 9p-linked families and several C9orf72 cohort descriptions [ 4, 5, 7, 12- 15, 20] suggested that psychosis (as defined by the presence of delusions or hallucinations of any type) might be a distinguishing feature of this mutation, data on psychotic symptoms will be presented separately; other symptoms will be discussed based on timing.
