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Results for “positional cloning”

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At least 163 records · Page 9Linked to original sources
PubMed1991

Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region.

Based on the map location of the aniridia (AN) locus in human chromosomal band 11p13, we have cloned a candidate AN cDNA (D11S812E) that is completely or partially deleted in two patients with AN. The less than 70 kb smallest region of overlap between the two deletions encompasses the 3' coding region of the cDNA. This cDNA, which spans over 50 kb of genomic DNA, detects a 2.7 kb message specifically within all tissues affected in AN. The predicted polypeptide product possesses a paired domain, a homeodomain, and a serine/threonine-rich carboxy-terminal domain, structural motifs characteristic of certain transcription factors. The concordance between expression and pathology, map location, structure, and predicted function argues that the cDNA corresponds to the AN gene.

Amino Acid Sequence↗
PubMed1994

X-linked adrenoleukodystrophy gene: identification of a candidate gene by positional cloning.

Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder characterized by a progressive demyelination of the central nervous system, adrenal insufficiency and impaired capacity to o-oxidase very long chain fatty acids, a metabolic process that normally takes place in peroxisomes. The ALD locus has been mapped to Xq28 and we have recently identified a patient with ALD who has a complex rearrangement in the 5' end of the red/green color pigment genes in Xq28. This rearrangement comprises two deletions separated by a large inversion. The second deletion of this key ALD patient extends 19 kb into the 3' region of an expressed gene which was found partially deleted in six of 85 independent patients with ALD. This segment thus constitutes a candidate region for the ALD gene.

Adolescent↗
PubMed1995

Positional cloning reaches maturity.

The identification of genes involved in human genetic disease is no longer the province of those who would make a career of 'not finding' a gene. Developments from the human genome initiative have vastly facilitated the process of localizing genetic intervals segregating mutations, as well as that of obtaining the physical regents necessary for characterizing the region. In a few years' time, efforts aimed at the assignment of genes to the physical map, coupled with increasing quantities of sequence data from both cDNA and genomic sources, will provide numerous candidate genes for analysis, with consequences for the approaches used to define the gene and mutations(s) involved in the disease of interest.

Animals↗
PubMed1993

Methods for finding genes. A major rate-limiting step in positional cloning.

Identification of transcribed sequences from within genomic regions has been a major rate-limiting step in the pursuit of genes involved in many human genetic diseases. Early efforts focused primarily on screening of cDNA libraries, identification of evolutionarily conserved sequences, and northern blot hybridization. In recent years, several innovative techniques for gene identification have been devised. These techniques expand the size of the genomic region capable of being scanned for genes, while also allowing detection of genes regardless of their expression patterns. This article reviews several new and older techniques and discusses the advantages and limitations of each.

Cloning, Molecular↗
PubMed2004

Genome scan analyses and positional cloning strategy in IBD: successes and limitations.

The past decade has witnessed a tremendous expansion of our knowledge-base of genetics of inflammatory bowel disease. To a large extent, this progress reflects the scientific innovation and impact of the human genome project, which has fueled many laboratory-based studies focusing on the molecular genetics of Crohn's disease and ulcerative colitis. The complementary strategies of genome-wide linkage scanning and candidate gene analysis uncovered a number of genetic loci associated with IBD susceptibility. Notably, the identification of the IBD1 and IBD5 loci is a major scientific discovery. Although many issues related to the function and expression of these genes await elucidation, there is a shared optimism that pivotal clinical applications will emerge from these investigations.

Carrier Proteins↗
PubMed2004

Positionally cloned susceptibility genes in allergy and asthma.

After several years of research to find asthma-susceptibility genes using genome-wide linkage scans and refined genetic mapping methods, four highly interesting candidate genes have recently been reported. Each of these genes represents a different functional class, and might point to a new pathway in the pathogenesis of asthma. Current research is focusing on confirming the genetic associations in diverse populations and understanding the biochemical functions of the proteins. These second-generation candidate genes for asthma susceptibility will stimulate much research, and might also enable the testing of multigenic models with sufficiently large sample sets.

ADAM Proteins↗
PubMed2004

A first generation physical map of the medaka genome in BACs essential for positional cloning and clone-by-clone based genomic sequencing.

In order to realize the full potential of the medaka as a model system for developmental biology and genetics, characterized genomic resources need to be established, culminating in the sequence of the medaka genome. To facilitate the map-based cloning of genes underlying induced mutations and to provide templates for clone-based genomic sequencing, we have created a first-generation physical map of the medaka genome in bacterial artificial chromosome (BAC) clones. In particular, we exploited the synteny to the closely related genome of the pufferfish, Takifugu rubripes, by marker content mapping. As a first step, we clustered 103,144 public medaka EST sequences to obtain a set of 21,121 non-redundant sequence entities. Avoiding oversampling of gene-dense regions, 11,254 of EST clusters were successfully matched against the draft sequence of the fugu genome, and 2363 genes were selected for the BAC map project. We designed 35mer oligonucleotide probes from the selected genes and hybridized them against 64,500 BAC clones of strains Cab and Hd-rR, representing 14-fold coverage of the medaka genome. Our data set is further supplemented with 437 results generated from PCR-amplified inserts of medaka cDNA clones and BAC end-fragment markers. Our current, edited, first generation medaka BAC map consists of 902 map segments that cover about 74% of the medaka genome. The map contains 2721 markers. Of these, 2534 are from expressed sequences, equivalent to a non-redundant set of 2328 loci. The 934 markers (724 different) are anchored to the medaka genetic map. Thus, genetic map assignments provide immediate access to underlying clones and contigs, simplifying molecular access to candidate gene regions and their characterization.

Animals↗
PubMed2001

Listen carefully: positional cloning of an audiogenic seizure mutation may yield Frings benefits.

Neurologists have long sought to understand what precipitates individual seizures in epileptic patients. Studies of reflex epilepsies seem well suited to this task. In this issue of Neuron, Skradski et al. describe a mutation in a novel gene underlying audiogenic seizures in the Frings mouse, providing a valuable resource for elucidating the pathophysiological mechanisms of this inherited form of reflex epilepsy.

Animals↗
PubMed1998

Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome.

Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal-recessive disorder, characterized by massive proteinuria in utero and nephrosis at birth. In this study, the 150 kb critical region of NPHS1 was sequenced, revealing the presence of at least 11 genes, the structures of 5 of which were determined. Four different mutations segregating with the disease were found in one of the genes in NPHS1 patients. The NPHS1 gene product, termed nephrin, is a 1241-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules, which by Northern and in situ hybridization was shown to be specifically expressed in renal glomeruli. The results demonstrate a crucial role for this protein in the development or function of the kidney filtration barrier.

Amino Acid Sequence↗
PubMed1994

Positional cloning of the mouse obese gene and its human homologue.

The mechanisms that balance food intake and energy expenditure determine who will be obese and who will be lean. One of the molecules that regulates energy balance in the mouse is the obese (ob) gene. Mutation of ob results in profound obesity and type II diabetes as part of a syndrome that resembles morbid obesity in humans. The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot.

Adipose Tissue↗
PubMed1996

Positional cloning of the mouse retrovirus restriction gene Fv1.

Vertebrate evolution has taken place against a background of constant retrovirus infection, and much of the mammalian genome consists of endogenous retrovirus-like elements. Several host genes have evolved to control retrovirus replication, including Friend-virus-susceptibility-1, Fv1, on mouse chromosome 4 (refs 3, 4). The Fv1 gene acts on murine leukaemia virus at a stage after entry into the target cell but before integration and formation of the provirus. Although restriction is not absolute, Fv1 prevents or delays spontaneous or experimentally induced viral tumours. In vitro, Fv1 restriction leads to an apparent 50-1,000 fold reduction in viral titre. Genetic evidence implicates a direct interaction between the Fv1 gene product and a component of the viral preintegration complex, the capsid protein CA (refs 7-9). We have now cloned Fv1: the gene appears to be derived from the gag region of an endogenous retrovirus unrelated to murine leukaemia virus, implying that the Fv1 protein and its target may share functional similarities despite the absence of nucleotide-sequence homology.

Amino Acid Sequence↗