Report of the second international workshop on human chromosome 7 mapping 1994

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Report of the committee on the genetic constitution of chromosomes 7 and 8

The total number of gene loci on chromosome 7 is now 67, of which 42 have been either physically isolated or detected by hybridization with homologous sequences from other species. A more detailed report on these subjects will be given at HGM10. The total number of gene loci on chromosome 8 is now 39. The committee has also recorded 36 arbitrary DNA segments. There are no current suggested ARPs. A request is made for further data to resolve the localization of MOS (Moloney murine sarcoma viral (v-mos) oncogene homolog) which is presently recorded as 8q11 or q21.2.link_to_subscribed_fulltex

Report of the committee on the genetic constitution of chromosomes 7 and 8.

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Integrated genetic-map of human-chromosome-2

A framework genetic map of human chromosome 2 is described, integrating data from the Centre d'Étude du Polymorphisme Humain (CEPH) version 6 database, the CEPH chromosome 2 consortium database, the National Institute of Health (NIH)/CEPH Collaborative Mapping group and other laboratories. A comprehensive map is also presented, showing regional locations of a large number of additional loci. The framework map is used to identify an informative set of meiotic breakpoints within the CEPH families, and the utility of this information for mapping new markers is discussed. The degree of typing error within the data set is estimated, as are the sex-specific interference parameters. A location database for these genetic and additional cytogenetic data is constructed using algorithms which map genetic distances on to a physical scale, and the potential for this approach to aid the integration of genetic and physical data is examined

Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly.

Holoprosencephaly (HPE) is a genetically and phenotypically heterogenous disorder involving the development of forebrain and midface, with an incidence of 1:16,000 live born and 1:250 induced abortions. This disorder is associated with several distinct facies and phenotypic variability: in the most extreme cases, anophthalmia or cyclopia is evident along with a congenital absence of the mature nose. The less severe form features facial dysmorphia characterized by ocular hypertelorism, defects of the upper lip and/or nose, and absence of the olfactory nerves or corpus callosum. Several intermediate phenotypes involving both the brain and face have been described. One of the gene loci, HPE3, maps to the terminal band of chromosome 7. We have performed extensive physical mapping studies and established a critical interval for HPE3, and subsequently identified the sonic hedgehog (SHH) gene as the prime candidate for the disorder. SHH lies within 15-250 kilobases (kb) of chromosomal rearrangements associated with HPE, suggesting that a 'position effect' has an important role in the aetiology of HPE. As detailed in the accompanying report, this role for SHH is confirmed by the detection of point mutations in hereditary HPE patients.link_to_subscribed_fulltex

A combined analysis of D22S278 marker alleles in affected sib-pairs: Support for a susceptibility locus for schizophrenia at chromosome 22q12

Recently, unstable trinucleotide repeats have been shown to be the etiologic factor in seven neuropsychiatric diseases, and they may play a similar role in other genetic disorders which exhibit genetic anticipation. We have tested one polymerase chain reaction (PCR)-based and two hybridization-based methods for direct detection of unstable DNA expansion in genomic DNA. This technique employs a single primer (asymmetric) PCR using total genomic DNA as a template to efficiently screen for the presence of large trinucleotide repeat expansions. High-stringency Southern blot hybridization with a PCR-generated trinucleotide repeat probe allowed detection of the DNA fragment containing the expansion. Analysis of myotonic dystrophy patients containing different degrees of (CTG)n expansion demonstrated the identification of the site of trinucleotide instability in some affected individuals without any prior information regarding genetic map location. The same probe was used for fluorescent in situ hybridization and several regions of (CTG)n/(CAG)n repeats in the human genome were detected, including the myotonic dystrophy locus on chromosome 19q. Although limited at present to large trinucleotide repeat expansions, these strategies can be applied to directly clone genes involved in disorders caused by large expansions of unstable DNA. © 1996 Wiley-Liss, Inc.link_to_subscribed_fulltex