FSH receptor genotype is associated with pregnancy but not with ovarian response in IVF.

Two very common single nucleotide polymorphisms at positions 307 and 680 in exon 10 of the FSH receptor gene have been associated with ovarian response in IVF. This observational study evaluated the role of the FSH receptor genotype in the prediction of poor response and clinical pregnancy in IVF in comparison with other markers, such as age, basal FSH, anti-Müllerian hormone and antral follicle count. In addition, the in-vitro cAMP response towards recombinant FSH in cultured granulosa cells of patients with different FSH receptor genotypes was determined. A total of 105 IVF patients undergoing ovarian stimulation in a long suppression protocol were included in the study. The ovarian response was comparable between patients with different FSH receptor genotypes. Patients with polymorphism Ser/Ser had implantation and pregnancy rates that were three times higher compared with patients with polymorphism Asn/Asn. FSH receptor genotype was not associated with a poor response in IVF, but showed a positive association with pregnancy, independent of age. There was no difference in cAMP production in cultured granulosa cells of patients with different FSH receptor genotypes (n=62). It is concluded that FSH receptor genotype is associated with pregnancy in IVF, but not with ovarian response.

Rapid detection of genomic imbalances using micro-arrays consisting of pooled BACs covering all human chromosome arms.

A strategy is presented to select, pool and spot human BAC clones on an array in such a way that each spot contains five well performing BAC clones, covering one chromosome arm. A mini-array of 240 spots was prepared representing all human chromosome arms in a 5-fold as well as some controls, and used for comparative genomic hybridization (CGH) of 10 cell lines with aneusomies frequently found in clinical cytogenetics and oncology. Spot-to-spot variation within five replicates was below 6% and all expected abnormalities were detected 100% correctly. Sensitivity was such that replacing one BAC clone in a given spot of five by a BAC clone from another chromosome, thus resulting in a change in ratio of 20%, was reproducibly detected. Incubation time of the mini-array was varied and the fluorescently labelled target DNA was diluted. Typically, aneusomies could be detected using 30 ng of non-amplified random primed labelled DNA amounts in a 4 h hybridization reaction. Potential application of these mini-arrays for genomic profiling of disseminated tumour cells or of blastomeres for preimplantation genetic diagnosis, using specially designed DNA amplification methods, are discussed.

Linkage Relationships and Haplotype Variation of the Major Histocompatibility Complex Class I A Genes in the Cichlid Fish Oreochromis niloticus.

The haplochromine cichlid species flocks of the East African Great Lakes are one of the best examples of adaptive radiation. Analysis of genetic variation among these species provides valuable information on species relationships and timing of speciation events. Although the haplochromine cichlids generally display little genetic variation, the major histocompatibility complex (Mhc) genes have been found to be highly variable. A study of the linkage relationships of the Mhc class I A genes in the cichlid fish Oreochromis niloticus was therefore undertaken. Class I loci were identified, and their segregation in seven mothers and their haploid embryos was determined. In total, 56 class I A sequences were found among the seven families. A strong concordance of segregation was observed in five haplotypes among the embryos, indicating a close linkage of all loci. The number of loci per haplotype varied from 11 to 17, while the total number of distinct loci found among all families was 22. These findings show that all class I A loci are linked in a single genetic cluster in O. niloticus.