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BackgroundOculocutaneous albinism (OCA) is caused by a group of genetically heterogeneous inherited defects that result in the loss of pigmentation in the eyes, skin and hair. Mutations in the TYR, OCA2, TYRP1 and SLC45A2 genes have been shown to cause isolated OCA. No comprehensive analysis has been conducted to study the spectrum of OCA alleles prevailing in Pakistani albino populations.MethodsWe enrolled 40 large Pakistani families and screened them for OCA genes and a candidate gene, SLC24A5. Protein function effects were evaluated using in silico prediction algorithms and ex vivo studies in human melanocytes. The effects of splice-site mutations were determined using an exon-trapping assay.ResultsScreening of the TYR gene revealed four known (p.Arg299His, p.Pro406Leu, p.Gly419Arg, p.Arg278*) and three novel mutations (p.Pro21Leu, p.Cys35Arg, p.Tyr411His) in ten families. Ex vivo studies revealed the retention of an EGFP-tagged mutant (p.Pro21Leu, p.Cys35Arg or p.Tyr411His) tyrosinase in the endoplasmic reticulum (ER) at 37°C, but a significant fraction of p.Cys35Arg and p.Tyr411His left the ER in cells grown at a permissive temperature (31°C). Three novel (p.Asp486Tyr, p.Leu527Arg, c.1045-15 T > G) and two known mutations (p.Pro743Leu, p.Ala787Thr) of OCA2 were found in fourteen families. Exon-trapping assays with a construct containing a novel c.1045-15 T > G mutation revealed an error in splicing. No mutation in TYRP1, SLC45A2, and SLC24A5 was found in the remaining 16 families. Clinical evaluation of the families segregating either TYR or OCA2 mutations showed nystagmus, photophobia, and loss of pigmentation in the skin or hair follicles. Most of the affected individuals had grayish-blue colored eyes.ConclusionsOur results show that ten and fourteen families harbored mutations in the TYR and OCA2 genes, respectively. Our findings, along with the results of previous studies, indicate that the p.Cys35Arg, p.Arg278* and p.Gly419Arg alleles of TYR and the p.Asp486Tyr and c.1045-15 T > G alleles of OCA2 are the most common causes of OCA in Pakistani families. To the best of our knowledge, this study represents the first documentation of OCA2 alleles in the Pakistani population. A significant proportion of our cohort did not have mutations in known OCA genes. Overall, our study contributes to the development of genetic testing protocols and genetic counseling for OCA in Pakistani families.

The growth characteristics of a series of influenza A viruses in the turbinates and lungs of hamsters was measured: in addition, the susceptibility of hamsters to infection by these viruses was also determined. These two criteria were used to give estimates of the growth potential of influenza viruses in hamsters, and the results were related to the incidence of transmission of virus from inoculated hamsters to cage-contacts. The results showed that strains of influenza virus reported as virulent for man tended to grow to higher titres in hamster nasal washings and lungs; were more infective for hamsters when inoculated by the intranasal route; and showed a high incidence of spread to cage-contacts. The methods could provide valuable measurements of virus attenuation and transmissibility for man, and the further exploitation of these techniques could facilitate the production and licensing of live, attenuated influenza virus vaccines.

Physical mapping of the human prostate-specific membrane antigen gene (FOLH) has not been straightforward. Previously, localisations of this gene to either 11p11.2 or 11q14 have been described. This raised the possibility of the presence of more than one related FOLH gene in man. We now present detailed characterisation of the region around a FOLH gene in a 500-kb non-chimaeric YAC clone, putatively assigned to 11p11.2. This clone contains two known microsatellites, D11S1326 and D11S1357 which have been previously mapped unequivocally to the 11p11.2 region at 62.5 cM. This data strongly supports the original 11p11.2 localisation of FOLH. The YAC clone also has a putative EST at each of its ends and these have thus been physically positioned on this chromosome. However, the two regions previously highlighted at 11p11.2 and 11q14 are apparently extensively duplicated, as evidenced by the appearance of dual FISH signals with a number of different genomic probes selected across this 500-kb 11p11.2 region.