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J Weissenbach

Publications and source records attributed to J Weissenbach.

At least 271 records · Page 15Linked to original sources
PubMed1994

Congenital nephrotic syndrome of the Finnish type maps to the long arm of chromosome 19.

Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disease that is characterized by massive proteinuria and nephrotic syndrome at birth. CNF represents a unique, apparently specific dysfunction of the renal basement membranes, and the estimated incidence of CNF in the isolated population of Finland is 1 in 8,000 newborns. The basic defect is unknown, and no specific biochemical defect or chromosomal aberrations have been described. Here we report the assignment of the CNF locus to 19q12-q13.1 on the basis of linkage analyses in 17 Finnish families. Multipoint analyses and observed recombination events place the CNF locus between multiallelic markers D19S416 and D19S224, and the significant linkage disequilibrium observed suggests that the CNF gene lies in the immediate vicinity of the markers D19S224 and D19S220.

Cell Line↗
PubMed1994

The genetic locus for free sialic acid storage disease maps to the long arm of chromosome 6.

Salla disease (SD), or adult-type free sialic acid storage disease, is an autosomal recessive lysosomal storage disorder characterized by impaired transport of free sialic acid across the lysosomal membrane and severe psychomotor retardation. Random linkage analysis of a sample of 27 Finnish families allowed us to localize the SD locus to the long arm of chromosome 6. The highest lod score of 8.95 was obtained with a microsatellite marker of locus D6S286 at theta = .00. Evidence for linkage disequilibrium was observed between the SD locus and the alleles of three closely linked markers, suggesting that the length of the critical region for the SD locus is in the order of 190 kb.

Alleles↗
PubMed1994

Refining the position of Wilson disease by linkage disequilibrium with polymorphic microsatellites.

Wilson disease (WND) is an autosomal recessive disorder that is due to an inability of the liver to eliminate copper. Copper buildup in the liver, brain, kidney, and other tissues can result in liver cirrhosis, neurologic and psychiatric defects, and other problems. We have localized the disease-containing region to between D13S31 and D13S59, with > 70 multiply affected families, and have constructed a YAC contig of > 4.5 Mb that spans these loci and orders nine highly polymorphic microsatellites. Here we present an analysis of disequilibrium with markers in this interval and provide evidence for strong allelic associations between AFM084xc5 alleles and WND alleles in European, Middle Eastern, and East Asian populations. Significant but weaker allelic associations were also observed between WND alleles and alleles at D13S137 and D13S169. The strength of the association between AFM084xc5 and WND in all non-Sardinian populations combined (linkage-disequilibrium coefficient [phi] = .61) suggests that the number of mutations accounting for WND is less than expected on the basis of the variety of clinical symptoms that are observed.

Chromosomes, Human, Pair 13↗
PubMed1993

A first-generation physical map of the human genome.

Sets of ordered overlapping cloned genomic DNA fragments that span each of the human chromosomes are urgently needed for identification of human disease genes. Such a physical map also provides unique material to study the structure and function of the genome. We have therefore exhaustively analysed the CEPH yeast artificial chromosome (YAC) library, which contains 33,000 clones, whose insert size was individually determined. These YACs have an average length of 0.9 megabases and cover the equivalent of 10 haploid genomes. Several mapping techniques were combined to provide multiple sources of structural information for most of these clones. Finally, the library was screened with more than 2,000 genetic markers quasiuniformly distributed over 90% of the genome. These results should allow the scientific community to construct detailed maps of all human chromosomes. Moreover, we propose a data analysis strategy that produces a first-generation integrated map covering most of the human genome.

Chromosome Mapping↗
PubMed1993

A 4.5-megabase yeast artificial chromosome contig from human chromosome 13q14.3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus.

We have previously performed a genetic analysis of multiply affected families to map a locus responsible for Wilson disease (WND) to a 0.3-centimorgan (cM) region within chromosome 13q14.3, between D13S31 and D13S59. Here we describe the construction of a contig of approximately 4.5 Mb, which spans this region and extends from D13S25 to D13S59. This contig consists of 28 genomic yeast artificial chromosome (YAC) clones. Five critical crossover events have been defined in this interval in two unaffected (Centre d'Etudes du Polymorphisme Humain) and three WND families. The combination of sequence tagged site content mapping of YACs with both polymorphic and nonpolymorphic markers and recombination breakpoint mapping resulted in the following order of polymorphic markers: centromere-RB1-D13S25-AFM205vh2-D13S31-D13S22 7-D13S228-AFM238vc3-D13S133- AFM084xc5-D13S137-D13S169, D13S155-D13S59-telomere. The recombination/physical distance ratio varies from approximately 3000 kb per cM in the region between D13S31 and D13S25 to 6000 kb per cM in the region between D13S31 and D13S59. Three WND families exhibiting recombination between the disease locus and D13S31 or D13S59 were genotyped for additional markers in this region and further refined the location of the WND gene to between D13S155 and D13S133. Nine of the markers in this region of < 1 cM are polymorphic microsatellites (seven have observed heterozygosities of 70% or above) that will be extremely useful in prenatal and preclinical diagnosis of this disease. This physical map is an essential step in the isolation of the WND gene and is a framework for the identification of candidate genes.

Base Sequence↗
PubMed1993

Refined linkage map of chromosome 5 in the region of the spinal muscular atrophy gene.

The genetic map in the region of human chromosome 5 that harbors the gene for autosomal recessive forms of spinal muscular atrophy (SMA) has been refined by a multilocus linkage study in 50 SMA-segregating families. Among six markers spanning 8 cM for combined sexes, four were shown to be tightly linked to the SMA locus. Multipoint linkage analysis was used to establish the best estimate of the SMA gene location. Our data suggest that the most likely location for the SMA locus is between blocks AFM114ye7 (D5S465)/EF5.15 (D5S125) and MAP-1B/JK53 (D5S112) at a sex-combined genetic distance of 2.4 and 1.7 cM, respectively. Thus the SMA gene lies in the 4-cM region between these two blocks. This information is of primary importance for designing strategies for isolating the SMA gene.

Base Sequence↗
PubMed1993

A continuous linkage map of 22 short tandem repeat polymorphisms on human chromosome 12.

A continuous linkage map consisting of 22 short tandem repeat polymorphisms has been constructed for human chromosome 12 using 23 non-CEPH pedigrees. The markers were distributed at an average distance of 9.35 cM (3.1-33.9 cM). Eighteen of the markers could be positioned uniquely with a likelihood of > 1000:1. The physical locations of some of the markers suggest that the map covers 85-95% of the chromosome. This framework map of 18 markers has a female length of 213 cM and a male length of 131 cM. Female recombination frequencies were greater than male recombination frequencies except in the distal portion of the short arm. The map provides confirmatory evidence for orders established previously on CEPH pedigrees and uniquely positions 4 additional markers (CD4, ATPSB, D12S56, PLA2).

Chromosome Mapping↗
PubMed1993

High-density genetic map of the BRCA1 region of chromosome 17q12-q21.

To facilitate the positional cloning of the breast-ovarian cancer gene BRCA1, we constructed a high-density genetic map of the 8.3-cM interval between D17S250 and GIP on chromosome 17q12-q21. Markers were mapped by linkage in the CEPH and in extended kindreds in our breast cancer series. The map comprises 33 ordered polymorphisms, including 12 genes and 21 anonymous markers, yielding an average of one polymorphism every 250 kb. Twenty-five of the markers are PCR-based systems. The order of polymorphic genes and markers is cen-D17S250-D17S518-HER2-THRA1-RARA-D17S80 -KRT10-[D17S800-D17S857]-GAS- D17S856-EDH17B-D17S855-D17S859-D17S858-[++ +PPY-D17S78]-D17S183-EPB3-D17S579- D17S509-[D17S508-D17S190 = D17S810]-D17S791-[D17S181 = D17S806]-D17S797- HOX2B-GP3A-[D17S507 = GIP]-qter. BRCA1 lies in the middle of the interval, between THRA1 and D17S183. Markers from this map can be used to determine whether cancer is linked to BRCA1 in families, to evaluate whether tumors have lost heterozygosity at loci in the region, and to identify probes for characterizing chromosomal rearrangements from patients and from tumors.

Alleles↗
PubMed1993

Microsatellite polymorphisms and the genetic linkage map of the human genome.

The use of simple sequence repeats as polymorphic genetic markers has significantly facilitated the construction of reference maps of the human chromosomes and the mapping of mendelian genetic diseases. These markers display major advantages over other systems, including restriction fragment length polymorphisms and satellites, but also have some limitations.

Animals↗
PubMed1993

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy maps to chromosome 19q12.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has been recently reported as a cause of stroke. It is characterized, in the absence of hypertension, by recurrent subcortical ischaemic strokes, starting in early or midadulthood and leading in some patients to dementia. Magnetic resonance imaging and pathological examination show numerous small subcortical infarcts and a diffuse leukoencephalopathy underlaid by a non-arteriosclerotic, non-amyloid angiopathy. We performed genetic linkage analysis in two unrelated families and assigned the disease locus to chromosome 19q12. Multilocus analysis with the location scores method established the best estimate for the location of the affected gene within a 14 centimorgan interval bracketed by D19S221 and D19S222 loci.

Adult↗
PubMed1993

A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10.

Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut. Taking advantage of a proximal deletion of chromosome 10q (del 10q11.2-q21.2) in a patient with total colonic aganglionosis, and of a high-density genetic map of microsatellite DNA markers, we performed genetic linkage analysis in 15 non-syndromic long-segment and short-segment HSCR families. Multipoint linkage analysis indicated that the most likely location for a HSCR locus is between loci D10S208 and D10S196, suggesting that a dominant gene for HSCR maps to 10q11.2, a region to which other neural crest defects have been mapped.

Base Sequence↗
PubMed1993

A gene for familial hemiplegic migraine maps to chromosome 19.

Familial hemiplegic migraine is an autosomal dominant disorder of unknown pathogenesis in which the migrainous attacks are marked by the occurrence of a transient hemiplegia during the aura. While investigating CADASIL, mapped previously to chromosome 19, we observed that some patients had recurrent attacks of migraine with aura. Although the clinical and neuroimaging features of familial hemiplegic migraine differ markedly from CADASIL, we hypothesized that the same gene could be involved in the pathogenesis of both conditions. We chose two large pedigrees for linkage analysis of familial hemiplegic migraine. A maximum lod score > 8 was found with two markers that are also strongly linked to CADASIL. Multilocus linkage analysis suggested that the loci responsible for the two diseases reside within an interval of about 30 cM on chromosome 19.

Adolescent↗
PubMed1993

Autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q.

Autosomal dominant familial spastic paraplegia (FSP) is a degenerative disorder of unknown aetiology characterized by a progressive spasticity of the legs. Three families with autosomal dominant FSP of early onset were analysed in linkage studies using highly polymorphic microsatellite markers. Close linkage to a group of markers on chromosome 14q (maximum multipoint lodscore z = 10) was observed in one family. This chromosome 14q candidate region was entirely excluded in the two other families, providing evidence of genetic heterogeneity within a homogeneous clinical form of FSP.

Adult↗
PubMed1993

A linkage map of human chromosome 15 with an average resolution of 2 cM and containing 55 polymorphic microsatellites.

We have constructed a 2.0 centiMorgan (cM) resolution genetic linkage map for chromosome 15q that contains 55 polymorphic satellites and 3 RFLPs that have placed on the map with odds for order of at least 1,000:1. Genotypes from 67 polymorphic loci (64 polymorphic microsatellites) were used to construct the map. Nine genes are included in the 1,000:1 map and 37 markers have heterozygosities of at least 70%. The sex-equal map length is 128 cM and the largest genetic interval is 11 cM (15.5 cM on the female map). The female and male map lengths are 150 cM and 106 cM, respectively. The map was constructed with 'MultiMap' and is based on the CEPH reference pedigrees and includes over 12,000 new genotypes. A sub-set of 12 markers spanning the length of the linkage map were genotyped in a somatic cell hybrid panel with breakpoints that divided 15q into five segments. Cytogenetic placement agreed with the linkage positions for each of the microsatellites tested with the exception of one (ACTC) which failed to give consistent results. Ten spontaneous new mutations were identified from a subset of 42 polymorphic microsatellites (out of a total of 20,420 transmissions), giving an apparent observed spontaneous mutation rate of 5 x 10(-4) per locus. An integrated map of chromosome 15q was also constructed with the microsatellite markers described here and previously genotyped RFLP-based markers. The sex average map spans 144.7 cM with an average distance between unique map locations of 3.5 cM and a maximum intermarker distance of 11.5 cM. These genetic linkage maps can be considered baseline maps for 15q which will be useful for physical mapping and the localization of disease genes and other genes of interest.

Base Sequence↗
PubMed1993

Severe childhood autosomal recessive muscular dystrophy with the deficiency of the 50 kDa dystrophin-associated glycoprotein maps to chromosome 13q12.

We have recently demonstrated the specific deficiency for the 50 kDa dystrophin-associated glycoprotein (50DAG) in Algerian patients afflicted with severe childhood autosomal recessive muscular dystrophy with DMD-like phenotype (SCARMD). A similar disease affecting Tunisian patients was linked to chromosome 13q but the status of the 50DAG was not investigated. Here we show by linkage analysis of Algerian families that the genetic defect which leads, either directly or indirectly, to the deficiency of the 50DAG in skeletal muscle is localized to the proximal part of chromosome 13q. We have not found any evidence of genetic heterogeneity among the thirteen families studied. It remains to be demonstrated whether the 50DAG gene maps at 13q12, and to determine if it is mutated in this disease.

Child↗
PubMed1993

Evidence of genetic heterogeneity in the autosomal recessive adult forms of limb-girdle muscular dystrophy following linkage analysis with 15q probes in Brazilian families.

The autosomal recessive limb-girdle muscular dystrophies (LGMD) represent a heterogeneous group of diseases which may be characterised by one or more autosomal loci. A gene at 15q has recently been found to be responsible for a mild form of LGMD in a group of families from the isolated island of Réunion, now classified as LGMD2. Based on results of eight out of 11 large Brazilian LGMD families of different racial background (which were informative for the closest available probe to the LGMD2 gene), we confirmed linkage to the LGMD2 gene at 15q in two of these families and exclusion in six others. These data provide the first evidence of genetic heterogeneity for the autosomal recessive limb-girdle muscular dystrophies.

Brazil↗
PubMed1993

Genetic mapping in the Xp11.2 region of a new form of X-linked hypophosphatemic rickets.

Human X-linked dominant hypophosphatemic rickets (HPDR I) is characterized by hypophosphatemia, hyperphosphaturia, abnormal vitamin D metabolism, and rickets/osteomalacia. Two closely linked hypophosphatemic genes, hypophosphatemia (Hyp) and Gyro (Gy), are known on the mouse X chromosome. The Hyp phenotype is the equivalent of the human X-linked hypophosphatemia, while the human equivalent of the Gyro mouse has not been unambiguously identified. We observed an Italian four-generation pedigree with a new form of X-linked recessive hypophosphatemic rickets (XLRH). We demonstrated that HPDR I and XLRH are two different X-linked genes and that XLRH maps in the Xp11.2 region at 0% recombination fraction from the DXS1039 locus. We discuss this new finding in relation to the identification of the human equivalent of the Gyro mouse and to the recent mapping in Xp11.22 of another X-linked recessive renal disorder named Dent disease.

Adult↗