| dc.description.abstract | Background: Atopic Eczema (AE) is a common skin disease that results from a complex
interplay between genetic and environmental factors. It may be associated with other
atopic phenotypes including; asthma, hayfever and food allergy. The onset, typically in
early childhood, can affect any part of the body but often occurs in the flexures of the
elbows and knees.
Aim and hypothesis: The aim of this thesis was to investigate the genetics of AE in the
Bangladeshi families of East London to identify possible positive association with AE or
other atopic diseases. This involved investigating previously associated genes and also
novel genes mapping to regions showing suggestive linkage from a microsatellite genome
scan and data from a haplotype tagging SNP based Illumina based Array genotyping.
Methods: A total of 70 families (n=384) individuals were recruited via the Paediatric
dermatology Clinic at the Royal London Hospital. Three genes; FOXP3, SPINK5 and TNC
were assessed for genetic association with AE and other atopic phenotypes using a
combination of techniques, such as PCR, dHPLC, sequencing, and Taqman SNP assays.
FBAT software was used for statistical analysis.
Results and future work: Suggestive associations with AE and other allergic disorders
were identified in all genes examined however, none of these results remained significant
(p-value<0.05) after correcting for multiple testing. As part of this project, several novel
genes have been identified including TNC, JAK3 and KYNU. To follow up these promising
findings, replication studies could be conducted in other populations with AE in particular
by large case-control analyses. In addition, with the development of high throughput SNP
genotyping and, in particular, exome sequencing, the larger Bangladeshi families with
multiple AE affected could be investigated to identify AE-associated disease mutations | |
