Tayfun Özçelik

Rett syndrome: exclusion mapping following the hypothesis of germinal mosaicism for new X-linked mutations

SummaryThe hypothesis of germinal mosaicism in the unaffected mother of two half-sisters affected with Rett syndrome is postulated to explain the unusual recurrence of this genetic disorder affecting only females (1/10000); it might be caused by new X-linked mutations with lethality in male fetuses. The analysis of 34 X-linked restriction fragment length polymorphisms (RFLPs) in these two affected females and in their unaffected mother and half-brother, together with the reconstruction of phase for 15 informative RFLPs in somatic cell hybrids retaining a single X chromosome from each female, has made it possible to exclude some regions of the X chromosome as possible sites of the mutation(s) causing Rett syndrome.

Chromosomal mapping of brain-derived neurotrophic factor and neurotrophin-3 genes in man and mouse.

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF3) are two new members of the nerve growth factor gene family, which play important roles in the development and maintenance of the vertebrate nervous system. Here we describe the assignments of the BDNF and NTF3 gene loci to human and mouse chromosomes and discuss the evolutionary relationship of human chromosomes 11 and 12. BDNF has been mapped to human chromosome 11p15.5-p11.2 and to mouse chromosome 2, and NTF3 to human chromosome 12p and mouse chromosome 6.

Human chromosome 19 contains the neurotrophin-5 gene locus and three related genes that may encode novel acidic neurotrophins

Differentiation, survival, and function of the vertebrate neurons are controlled by multiple, target-derived neurotrophic factors. The best characterized mammalian neurotrophic factors are four structurally related 13 to 14 kDa basic proteins, collectively known as neurotrophins. Here we describe the identification of a gene cluster localized on human chromosome 19 that contains neurotrophin-5 (NT-5) and that may encode three additional acidic members of this protein family. The three novel partial open reading frames (ORFs), designated neurotrophin-6-α (NT6-α), NT6-β and NT6-γ, are 95% identical to each other and 75% identical to NT5. The putative matureN-terminal portion of NT6 ORFs does not contain a typical dibasic cleavage site and lacks two out of six cysteines that are conserved among the neurotrophins. The unique structures of NT6-α, -β, and -γ suggest that if the NT6 open reading frames indeed code for functional proteins, these proteins may display novel functions and may act through a distinct class of receptors. In the human, both NTF5 and NTF6 gene loci were mapped to chromosome 19 by Southern analysis of somatic cell hybrid panels. In mouse, the NT5 gene (Ntf-5) was assigned to chromosome 7 and no sequences representing NT6 homologs were identified.

Dlx2 (Tes1), a homeobox gene of the Distal-less family, assigned to conserved regions on human and mouse chromosomes 2

Dlx-2 (also called Tes-1), a mammalian member of the Distal-less family of homeobox genes, is expressed during murine fetal development in spatially restricted domains of the forebrain. Searching for a candidate neurological mutation that might involve this gene, we have assigned the human and mouse loci to regions of conserved synteny on human chromosome 2, region cen--q33, and mouse chromosome 2 by Southern analysis of somatic cell hybrid lines. An EcoRI dimorphism, discovered in common inbred laboratory strains, was used for recombinant inbred strain mapping. The results place Dlx-2/Tes-1 near the Hox-4 cluster on mouse chromosome 2.

Genomic landscape of the Greater Middle East

Study of the Greater Middle East (GME), home to approximately 10% of the worlds population, has made invaluable contributions to the characterization of rare genetic disease, especially recessive conditions arising from the tradition of consanguinity and large families with multiple children. A new study now reports 1,111 unrelated exomes from the GME and provides a comprehensive view of genetic variation for enhanced discovery of disease-associated genes.