The tyrosinase-positive oculocutaneous albinism locus maps to chromosome 15q11.2-q12.

Tyrosinase-positive oculocutaneous albinism (ty-pos OCA), an autosomal recessive disorder of the melanin biosynthetic pathway, is the most common type of albinism occurring worldwide. In southern African Bantu-speaking negroids it has an overall prevalence of about 1/3,900. Since the basic biochemical defect is unknown, a linkage study with candidate loci, candidate chromosomal regions, and random loci was undertaken. The ty-pos OCA locus was found to be linked to two arbitrary loci, D15S10 and D15S13, in the Prader-Willi/Angelman chromosomal region on chromosome 15q11.2-q12. The pink-eyed dilute locus, p, on mouse chromosome 7, maps close to a region of homology on human chromosome 15q, and we postulate that the ty-pos OCA and p loci are homologous.     

Comparative mapping of human Chromosome 14q11.2-q13 genes with mouse homologous gene regions

An examination of the synteny blocks between mouse and human chromosomes aids in understanding the evolution of chromosome divergence between these two species. We comparatively mapped the human (HSA) Chromosome (Chr) 14q11.2-q13 cytogenetic region with the intervals of orthologous genes on mouse (MMU) chromosomes. A lack of conserved gene order was identified between the human cytogenetic region and the interval of orthologs on MMU 12. The evolutionary breakpoint junction was defined within 2.5 Mb, where the conserved synteny of genes on HSA 14 changes from MMU 12 to MMU 14. At the evolutionary breakpoint junction, a human EST (GI: 1114654) with identity to the human and mouse BCL2 interacting gene, BNIP3, was mapped to mouse Chr 3. New gene homologs of LAMB1, MEOX2, NRCAM, and NZTF1 were identified on HSA 7 and on the proximal cytogenetic region of HSA 14 by mapping mouse genes recently reported to be genetically linked within the relevant MMU 12 interval. This study contributes to the identification of homology relationships between the genes of HSA 14q11.2-q13 and mouse Chr 3, 12, and 14. Received: 16 March 2000 / Accepted: 16 June 2000     

Comparative map between chicken Chromosome 15 and human chromosomal region 12q24 and 22q11-q12

The physical and comparative map of GGA15 was improved by the construction of 9 BAC contigs around loci previously mapped on GGA15 by linkage analysis. In total, 240 BAC clones were isolated, covering 30–35% of GGA15, and 120 STS were developed (104 STS derived from BAC end sequences and 18 STS derived within genes). Seventeen chicken orthologues of human genes located on human Chr 22q11-q12 were directly mapped within BAC contigs of GGA15. Furthermore, the partial sequences of the chicken BAC clones were compared with sequences present in the EMBL/GenBank databases and revealed matches to 26 genes, ESTs, and genomic clones located on HSA22q11-q12 and HSA12q24. These results provide a better alignment of GGA15 with the corresponding regions in human and mouse, and improve our knowledge of the evolution and dynamics of the vertebrate genome. GenBank Accession Numbers: The nucleotide sequence data reported in this paper have been submitted to GenBank and have been assigned the accession numbers BZ592394-BZ592544.     

Localization of monocyte chemotactic protein-1 gene (SCYA2) to human chromosome 17q11.2-q21.1

Monocyte chemotactic protein-1 (MCP-1) is a member of the small inducible gene (SIG) family. It has been shown to play a role in the recruitment of monocytes to sites of injury and infection. By analysis of a panel of somatic cell hybrids, we have localized the MCP-1 gene, designated SCYA2, to human chromosome 17. In situ hybridization confirmed this assignment and further localized the gene to 17q11.2-q21.1.     

A locus for brachydactyly type A-1 maps to chromosome 2q35-q36

Brachydactyly type A-1 (BDA1) was, in 1903, the first recorded example of a human anomaly with Mendelian autosomal dominant inheritance. Two large families, the affected members of which were radiographed, were recruited in the study we describe here. Two-point linkage analysis for pedigree 1 (maximum LOD score [Zmax] 6.59 at recombination fraction [theta] 0.00) and for pedigree 2 (Zmax=5.53 at straight theta=0.00) mapped the locus for BDA1 in the two families to chromosome 2q. Haplotype analysis of pedigree 1 confined the locus for family 1 within an interval of <8.1 cM flanked by markers D2S2248 and D2S360, which was mapped to chromosome 2q35-q36 on the cytogenetic map. Haplotype analysis of pedigree 2 confined the locus for family 2 within an interval of <28. 8 cM flanked by markers GATA30E06 and D2S427, which was localized to chromosome 2q35-q37. The two families had no identical haplotype within the defined region, which suggests that the two families were not related.     

The human homolog of the mouse common viral integration region, FLI1, maps to 11q23-q24.

FLI1 is a common mouse viral integration region in virus-induced leukemias and lymphomas. Using an evolutionarily conserved mouse probe and Southern hybridization to (rodent x human) somatic cell hybrid DNAs, the human homolog of FLI1 has been shown to lie on a fragment of chromosome 11 flanked on the centromeric side by the acute lymphoblastic leukemia-associated t(4;11)(q21;q23) translocation breakpoint and on the telomeric side by the Ewing- and neuroepithelioma-associated t(11;22) (q24;q12) breakpoint.     

A locus for autosomal dominant colobomatous microphthalmia maps to chromosome 15q12-q15

Congenital microphthalmia is a common developmental ocular disorder characterized by shortened axial length. Isolated microphthalmia is clinically and genetically heterogeneous and may be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Here, we studied a five-generation family of Sephardic Jewish origin that included 38 members, of whom 7 have either unilateral or bilateral microphthalmia of variable severity inherited as an autosomal dominant trait with incomplete penetrance. After exclusion of several candidate loci, we performed a genome-scan study and demonstrated linkage to chromosome 15q12-q15. Positive LOD scores were obtained with a maximum at the D15S1007 locus (maximum LOD score 3.77, at recombination fraction 0.00). Haplotype analyses supported the location of the disease-causing gene in a 13.8-cM interval between loci D15S1002 and D15S1040.     

Neural retina-specific leucine zipper gene NRL (D14S46E) maps to human chromosome 14q11.1-q11.2.

The product of a neural retina-specific gene, NRL, belongs to the "leucine zipper" family of DNA-binding proteins and has a strong similarity to the v-maf oncogene product. The NRL gene maps to human chromosome 14 by Southern blot analysis of genomic DNA from a human-rodent somatic cell hybrid panel. In situ hybridization to metaphase chromosomes has further sublocalized the gene to the region 14q11.1-q11.2. D14S46E has now been assigned to the NRL gene. Because of its specific pattern of expression, NRL is a candidate gene for retinal diseases.     

Chromosome localization of two human serine protease genes to region 14q11.2----q12 by in situ hybridization

Two human serine protease genes have been cloned. One corresponds to CTLA1, the human equivalent of the mouse cytotoxic cell protease gene Ctla-1, and the other is novel. Both genes were localized to 14q11.2----q12 by in situ hybridization. This result confirms the assignment of human CTLA1 to 14q11.2----q12 and provides new mapping data for another human serine protease gene located in the same chromosome region.     

The stumbler mutation maps to proximal mouse Chromosome 2

The cerebellar mouse mutation stumbler (stu) was mapped to proximal Chromosome (Chr) 2 with a recently developed polymerase chain reaction assay for endogenous retroviruses that vary between mouse strains. The stu locus resides between the markers D2Mit5 and D2Mit7. A number of developmentally or neurologically relevant candidate genes map in this region, including Bmi1, Dbh, Grin1, Notch1, Pax8, Rxra, and Spna2. Knowing the chromosomal localization of stu should simplify maintenance of the stumbler mouse stock and also enable analysis of the cerebellar defect in presymptomatic individuals.