2011 YÜksek lisans tez özetleri

Development Of CGH Based Microarray Kit Intended For Diagnosis Of Premature Ovarian Failure (POF)

Premature ovarian failure (POF) is defined as amenorrhoea for more than six months in the presence of elevated gonadotropins and FSH serum level higher than 40 U/L, occurring before the age of 40. Female infertility is presently an irreversible consequence of POF. POF and prolonged estrogen deficiency may lead to the early onset of osteoporosis. The early diagnosis of familial POF will provide the opportunity to predict the likelihood of early menopause, and allow other reproductive choices to be made, such as freezing embryos or having children earlier. Premature Ovarian Failure (POF) syndrome is a very heterogeneous clinical disorder due probably to complex genetic networks controlling human folliculogenesis. Some experimental evidence suggests that these genes might be clustered on the female sex chromosome in the POF1 (Xq26.2-q28) and POF2 (Xq13.3-q22) loci. The genes such FMR1, HS6ST2, TDPF3, GPC3 in POF1 locus and DIAPH2, DACH2, POF1B in POF2 locus were identified as POF candidate genes. However, mutations on some autosomal genes like AIRE, DAZL, FOXL2, FSHR, GALT and GDF9, INHα members of TGF-β gene family are also estimated to play a role in POF pathology. Currently, “Microarray” CGH appears as a current method of investigation for mutation analysis of genes. Also, the results can be taken more rapidly and analysis phase can be performed full automatically with this method. “Microarray” CGH approach enables the analysis of whole genome range chromosomal losses or gains in a short time and with high-resolution.

In the current study, it is aimed to develop a “microarray” CGH including multiple copies of POF candidate genes that exist on the X and autosomal chromosomes. Thus, it can be contributed prevalent applicability of this method which is more sensitive, simple applied, fast and low cost according to the existing technologies. For this purpose, we have designed a POF-specific microarray kit which consists of 413 genomic clones (393 “Bacterial Artificial Chromosomes” (BACs) and 20 “P1 derived Artificial Chromosomes” (PACs) ) spotted in four copies that contains totally 1824 spots with control regions for the each array slide.