| title: | HUMAN LUTEINIZING HORMONE/CHORIONIC GONADOTROPIN ß-SUBUNIT GENOME CLUSTER: (I) The role of non-homologous crossing-over and gene conversion in shaping the genetic variation and LD structure (II) Distribution of allelic/ haplotypic variation and expression profile of CGB genes in normal versus recurrently miscarriaged pregnancy |
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| reg no: | ETF5796 |
| project type: | Estonian Science Foundation research grant |
| subject: |
1.8. Molecular Biology 3.1. Basic Medicine |
| status: | accepted |
| institution: | TU Faculty of Biology and Geography |
| head of project: | Maris Laan |
| duration: | 01.01.2004 - 31.12.2007 |
| description: | During the last 10 years the focus of human genetics has been shifting from analyzing monogenetic diseases towards studies on the genetic background of complex traits. The prerequisite for successful association studies is the understanding of the factors shaping human genome variation and the extent of LD (linkage disequilibrium). The role of gene conversion (GC) in shaping human genome has been often overlooked. The proposed project aims a detailed analysis on one of the genome regions prone to GC - LHB/CGB gene cluster. This region consist of 7 genes (1 LHB, 6 CGB), which have evolved through tandem segmental duplications at the primate lineage. The following aspects are studied: (1) the role of GC on the extent of LD and creating new haplotypes; (2) the cross-over activity, frequency of GC and length of GC tract by using the sperm DNA analysis; (3) comparison of human and chimpanzee LHB/CGB genome cluster to understand the role of GC in the evolution of gene(familie)s. The proposed project is interdisciplinary. The detailed background knowledge gathered during the analysis of the LHB/CGB cluster is applied in a study of clinical genetics context. The hypothesis is proposed for the association of recurrent spontaneous abortions with polymorhic variants of CGB genes, which might hinder the expression, or assembly and activity of hCG. hCG hormone has the major role in implantation during the first trimester. However, it is not known whether CGB genes (1) are imprinted or transcribed from both parental chromosomes; (2) are all co-expressed or exhibit expressional variation. (3) How the polymorhic (allelic/haplotypic/structural) variants for CGB genes influence the of hCG activity. From the patient point of view, this study might improve the therapy of habitual abortions. Several clinical studies have shown that repeated treatment with hCG reduced the chance for a spontaneous abortion. The haplotyping of CGB genes and understanding the clinical context of the CGB variants would enable to offer the patients more personalized medicine.¿¿¿¿¿ |
| project group | ||||
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| no | name | institution | position | |
| 1. | Maris Laan | TU Faculty of Biology and Geography | senior scientist | |