gene mapping

watchman watchman at
Sun Aug 12 17:01:34 EST 2001

I am hoping someone maybe able to answer a question?

Am I making a 'stretch'.. here?

These two articles speak to different diseases.
Ther first article speaks to a hypothesis placed recently in 
which he finds cystic fibrosis to be linked to hemochromatosis..through
the .. HLA ..
The second article ALSO mentions the .. HLA .. and since I am an 
idiot .. I am hoping someone may be able to tell me if this 
'sugggests' therefore .. a 'possible' link from hemochromatosis 
TO .. gastrointestinal problems?

Subject: HLA/hemochromatosis

   Genet Test 1998;2(1):85-8
Is the hemochromatosis gene a modifier locus for cystic fibrosis?

    Rohlfs EM, Shaheen NJ, Silverman LM
   Department of Pathology & Laboratory Medicine, University of North
   Carolina, Chapel Hill 27599, USA.
   The variable clinical manifestations of cystic fibrosis (CF) suggest
   the influence of modifier genes. For example, meconium ileus is
   present in approximately 10-15% of neonates with cystic fibrosis;
   however, the genetic and, or environmental factors that determine
   whether an individual will develop this complication have not been
   determined. We propose the HFE gene as a candidate modifier locus for
   CF based on (1) the suggestion of an association between the HLA loci
   and CF phenotypes; 
   (2) the location of the HFE gene near the HLA loci
   and; (3) the similarity between the gastrointestinal manifestations of
   hereditary hemochromatosis and CF. We have determined the frequency of
   the C282Y and H63D mutations in a group of 89 CF patients who were
   homozygous for delta F508 and for whom meconium ileus status was
   known. The carrier frequency of C282Y among the CF patients with
   meconium ileus was significantly different from that of our unaffected
   control group (19.4% versus 7.7%). However, the difference between the
   meconium ileus and the nonmeconium ileus groups was not significant
   (19.4% versus 10.3%). There was no difference in the frequency of the
   H63D among the three groups that were studied. These data are
   suggestive of a relationship between the development of meconium ileus
   or other gastrointestinal diseases in CF and the HFE gene. Further
   study of a larger group of patients is warranted.
   PMID: 10464603, UI: 99393869
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Subject: HLA/crohn/colitis

   Aliment Pharmacol Ther 2001 Jun;15(6):731-48
The genetics of inflammatory bowel disease.

    Ahmad T, Satsangi J, McGovern D, Bunce M, Jewell DP
   Gastroenterology Unit, Radcliffe Infirmary, Oxford, UK Department of
   Gastroenterology, Western General Hospital, Edinburgh, UK Tissue
   Typing Laboratory, Churchill Hospital, Oxford, UK.
   [Medline record in process]
   Recent epidemiological, clinical and molecular studies have provided
   strong evidence that inherited predisposition is important in the
   pathogenesis of chronic inflammatory bowel diseases. The model most
   consistent with the epidemiological data suggests that Crohn's disease
   and ulcerative colitis are related polygenic diseases, sharing some
   but not all susceptibility genes. Investigators throughout the world
   have applied the complementary techniques of genome-wide scanning and
   candidate gene analysis. Four areas of linkage have been widely
   replicated on chromosomes 16 (IBD1), 12 (IBD2), 

   6 (IBD3-the HLA region), 
   and most recently on chromosome 14. Fine mapping of these
   regions is underway. Of the 'positional' candidate genes, most
   attention has centred on the genes of the major histocompatibility
   complex. Genes within this region may determine disease
   susceptibility, behaviour, complications and response to therapy. Hope
   continues that studies of inflammatory bowel disease genetics will
   provide fresh insight into disease pathogenesis and soon deliver
   clinical applications.
   PMID: 11380312, UI: 21275015

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