Positional Cloning of Disease Causing Genes [Elektronisk resurs] A Genetic Study of Obesity, Ichthyosis Prematurity Syndrome and Meniere's Disease

• Positional cloning is a method to identify genes from their position in the genome without prior knowledge about function. We used this approach to investigate the basis for three distinct genetic disorders; Obesity, Ichthyosis Prematurity Syndrome and Meniere's disease. Obesity appears when energy intake exceeds energy expenditure which leads to an abnormal accumulation of fat in the adipocyte tissue. We have studied a family with a balanced chromosomal translocation t(4;15) segregating with severe obesity. The chromosomal breakpoints create a fusion gene involving the gene for isoform 1 of RAR-related orphan receptor A ( RORa1 ) which is implicated in the regulation of adipogenesis and lipoprotein metabolism. We hypothesize that the obesity in this family is caused by haploinsufficiency of this gene or a gain of function of the fusion gene. Ichthyosis prematurity syndrome (IPS) is a rare skin disorder belonging to a group of autosomal recessive congenital ichthyosis. We have mapped the locus for IPS to chromosome 9q34. Within the IPS locus, we identified a core haplotype with a high carrier frequency among affected, which indicate a possible founder mutation for the disease. The minimal shared region in affected patients contains seven genes which are candidates for IPS. Meniere's disease (MD) is characterised by spontaneous attacks of vertigo, fluctuating sensorineural low frequency hearing loss, aural fullness, and tinnitus. We mapped the MD locus to chromosome 12p13 using three Swedish families. The linked region is 463 kb, containing only one gene, a phosphoinositide-3-kinase ( PIK3C2G ). Involvement of phosphatidylinositol 3-kinases (PI-3K) in the intra cellular signalling cascades of cells in mammalian balance epithelia makes this gene a good candidate gene for MD. 

Ämnesord

Medical and Health Sciences  (hsv)

Basic Medicine  (hsv)

Medical Genetics  (hsv)

Medicin och hälsovetenskap  (hsv)

Medicinska och farmaceutiska grundvetenskaper  (hsv)

Medicinsk genetik  (hsv)

MEDICINE  (svep)

Dermatology and venerology,clinical genetics, internal medicine  (svep)

Clinical genetics  (svep)

MEDICIN  (svep)

Dermatologi och venerologi, klinisk genetik, invärtesmedicin  (svep)

Klinisk genetik  (svep)

Genre

government publication  (marcgt)

Indexterm och SAB-rubrik

Genetics

Positional cloning

Obesity

Ichthyosis

Meniere’s disease

RORa

PIK3C2G

Genetik