<p>The aim of this thesis has been to identify genes and gene regions underlying four different disorders. In papers I-IV, positional cloning methods, such as linkage, association and haplotype analysis have been used for the identification of genomic regions associated with the ichthyosis prematurity syndrome (IPS), adult-onset autosomal dominant leukodystrophy (ADLD) and Kostmann disease. </p><p>IPS is a rare autosomal recessive skin disorder, which includes a premature birth of the affected child. We mapped the IPS locus to a region on chromosome 9q34, and within this region a haplotype is shared by IPS patients, which suggests a strong founder effect. The haplotype spans 76 kb, which includes four known genes. No sequence or mRNA expression alterations could be detected for the four genes in IPS patients. </p><p>A candidate region for an adult-onset leukodystrophy (ADLD) on chromosome 5 was investigated in a large Swedish family with ADLD. A significant multipoint LOD score of 9.45 was obtained for markers in the chromosome 5 region and fine-mapping of recombination events restricts a candidate gene region to 1.5 Mb. </p><p>Kostmann disease is an autosomal recessive form of severe congenital neutropenia. We have identified a 1.2 Mb region on chromosome 1q22 associated with the disease in the original Kostmann family. The region contains 37 genes.</p><p>In paper V, cDNA microarrays were used to asses the mRNA levels of 7,700 genes in lymphoblastoid cell lines derived from autistic and control samples. The <i>SEMA5A</i> gene, which is involved in axonal guidance, was found downregulated in the cells derived from autistic individuals, and this was confirmed by quantitative PCR. </p><p>In summary, candidate genes or gene regions have been identified for all four disorders and further studies are needed to confirm their roles in the pathogenesis of the disorders. </p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-7344 |
| Date | January 2006 |
| Creators | Melin, Malin |
| Publisher | Uppsala University, Department of Genetics and Pathology, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 207 |
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