The development of genetic linkage maps in farm animals is progressing rapidly. Linkage maps can be used to identify genetic loci responsible for genetic variation in traits of economic importance. The ultimate goal is to find the underlying genes involved in these traits. To achieve this, the so called positional candidate gene approach is gaining in importance. This approach is based on the genetic localization of a trait using genetic linkage analysis in livestock species. Subsequent comparative mapping of the trait locus with the gene-rich maps of the human and the mouse may reveal candidate genes for the trait in question.
For the construction of comparative maps the genetic localization of many genes needs to be determined. In this thesis, the development of highly informative microsatellite markers from expressed sequences, derived from a brain and embryonic cDNA library of the chicken, is described. In addition to this, a preliminary comparative map of the chicken is presented.
The second objective of this thesis was to develop a quick and reliable method in order to localize monogenic traits. To achieve this, an already existing technique, called bulked segregant analysis, which has originally been used for the localization of monogenic traits in plants using random amplified polymorphic DNA markers (RAPDs), and restriction fragment length polymorhisms (RFLPs), was combined with the use of fluorescently labelled microsatellite markers. This method prooved to be very sensitive in detecting linked markers at greater genetic distances and the genetic map locations of the monogenic traits Dominant White ( I ) and Autosomal dwarfism ( adw ) were succesfully determined.
Comparative mapping revealed that adw is located in a chromosomal region that is conserved between chicken, human and mouse. Interestingly, in the mouse the phenotype "Pygmy" , which shows a striking similarity to the Autosomal Dwarf phenotype in chickens, is also located in this region. The Pygmy phenotype arises from the inactivation of the High Mobility Group I-C ( HMGI-C ) gene. In the human, the HMGI-C gene is also located in the same conserved chromosomal segment. Fluorescent in situ hybridization of chicken metaphase chromosomes using the chicken HMGI-C gene as a probe, showed that the chicken HMGI-C gene is indeed located in the region of the adw locus. However, northern blot analysis showed no difference in the expression of the HMGI-C gene between adw and wild type chicken embryos. Also no mutations in the HMGI-C mRNA were detected. Finally, other candidate genes for both adw and I are proposed.
|Qualification||Doctor of Philosophy|
|Award date||13 Oct 1998|
|Place of Publication||S.l.|
|Publication status||Published - 1998|
- gene mapping
- genetic markers
- nucleotide sequences
- gene expression
- insulin-like growth factor