Conclusions

Although all the genes in the chromosome 6 candidate gene were sequenced no mutations were discovered. This implies that there may be more genes in this region that have yet to be identified, although analysis of the human mRNAs expressed here reveals only a few other aligned mRNA sequences that did not correspond to the known genes. The mutational analysis we performed was PCR-based and this method could have failed to detect any genomic deletions that could cause hap-loinsufficiency or larger in-frame and potentially dominant-acting deletions. Obtaining skin biopsy samples from patients and quantifying the expression of these genes by quantitative RT-PCR to accurately measure expression of alleles could overcome this problem. Seemingly benign missense mutations and polymorphisms should also not be overlooked. These types of changes have recently been discovered to affect splicing and have been shown to cause breast cancer and cystic fibrosis [39, 46].

The candidate region on chromosome 19 covered a large area, 16.8 Mb of genomic sequence. There were relatively few genes in comparison to the size of the region and the fact that chromosome 19 is one of the most gene-rich chromosomes [58]. The candidate region links over the centromere and the regions immediately adjacent to the centromere are not predicted to contain many genes. The linked region, defined by markers D19S911 and D19S1170, was rich in ZNF genes and chromosome 19 has the highest repeat density [58]. The majority of the ZNF proteins are highly expressed in T lymphoid cells, B-cells and monocytic and erythroid cells. Although the functions of most are unknown, as a whole, ZNF proteins are thought to be involved in development. ZNF91 has been shown to function as a repressor of an IgG receptor and therefore has an influence on the immune response as do some of the other candidate genes studied, such as TIZ. No mutation was found in any of the candidate genes analysed but there are a number of genes still to be sequenced. In addition to the known genes, mRNA alignment and gene predictions reveal that there may still be some genes that are as yet unidentified.

In conclusion, the first two candidate genetic loci for HS have been identified and this will form the basis of future genetic studies, using other families with clearly defined dominant inheritance, to narrow down these loci and identify the causative genetic lesions. Importantly, a number of other families do not link to either locus. These families were too small to perform genome-wide linkage analysis but it demonstrates that HS is indeed a genetically heterogeneous disease with potentially three or more genes involved in its molecular pathogenesis. The eventual identification of these causative genes will undoubtedly be of benefit in understanding the pathomechanisms of HS and form the basis for a rational design of new therapeutic strategies.

How To Reduce Acne Scarring

How To Reduce Acne Scarring

Acne is a name that is famous in its own right, but for all of the wrong reasons. Most teenagers know, and dread, the very word, as it so prevalently wrecks havoc on their faces throughout their adolescent years.

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