RESUMEN
32 families informative for the segregation of Tuberous sclerosis (TSC) have been examined for genetic markers on chromosomes 9, 11, 12 and 16. In one large family there was clear evidence of linkage to markers on chromosome 16p13.3 (lodscore with D16S291 of 4.7 at theta = 0) but other families were too small to give individually convincing lodscores. Combined results for all families gave positive results with ABO/DBH on chromosome 9 (max lod 2.63) and with D16S291 on chromosome 16 (max lod 3.98) at values of theta of 0.2 in each case. Further analysis showed strong evidence for heterogeneity with approximately half the families linked to a locus TSC1 on chromosome 9 between ASS and D9S298 and half to TSC2 on chromosome 16 close to D16S291. There was no definite support for a third locus although in many families this could not be excluded. In three families the segregation pattern of TSC remains unexplained. In two of these the family apparently segregates for TSC1 but in each case a single affected individual appeared to exclude the whole of the candidate region. Preliminary analysis of clinical features did not reveal any definite differences in incidence of mental handicap between individuals in different linkage groups or with different sex of the parent of origin. The frequencies of periungual fibromas and facial angiofibromas were also similar in both linkage groups. The difficulties of detecting linkage in small families where there is locus heterogeneity are discussed. The program ZZ was found to be helpful in this respect.
Asunto(s)
Cromosomas Humanos Par 16 , Cromosomas Humanos Par 9 , Ligamiento Genético , Esclerosis Tuberosa/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Mapeo Cromosómico , Femenino , Humanos , Lactante , Escala de Lod , Masculino , Persona de Mediana EdadRESUMEN
This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of chromosome 2. The map contains 36 loci defined by genotyping generated from the CEPH family DNAs. A total of 73 different markers were typed by 14 contributing laboratories; of these, 36 loci are ordered on the map with likelihood support of at least 1000:1. Markers are placed along the length of the chromosome but no markers were available to anchor the map at either telomere or the centromere. Multilocus linkage analysis has produced male, female, and sex-averaged maps extending for 261, 430, and 328 cM, respectively. The sex-averaged map contains five intervals greater than 15 cM and the mean genetic distance between the 36 uniquely placed loci is 9.1 cM.
Asunto(s)
Cromosomas Humanos Par 2 , Ligamiento Genético , Mapeo Cromosómico , ADN , HumanosAsunto(s)
Mapeo Cromosómico , Cromosomas Humanos , Ligamiento Genético , Humanos , Recombinación GenéticaRESUMEN
The first CEPH consortium map, that of chromosome 10, is presented. This primary linkage map contains 28 continuously linked loci defined by genotypes generated from CEPH family DNAs with 37 probe and enzyme combinations. Cytogenetic localization of some of the genetic markers indicates that the consortium map extends, at least, from 10p13 to 10q26. The order of loci on the consortium map agrees with the physical localization data. The female map spans 309 cM (206 cM if an approximation of interference is included in the mapping function used to construct the map), and the mean genetic distance of intervals is 11 cM (7 cM). Also presented are maps of chromosome 10 from each of five CEPH collaborating laboratories, based on genotypes for all relevant markers in the CEPH database. The CEPH consortium map of chromosome 10 should be useful for localization of any gene of interest falling within the span covered. The genotypes in the chromosome 10 consortium map database are now available to the scientific community.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 10 , Cromosomas Humanos Par 10/ultraestructura , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Masculino , Estudios Multicéntricos como Asunto , Polimorfismo de Longitud del Fragmento de Restricción , Recombinación GenéticaRESUMEN
Mapping started exactly 50 years ago when Bell & Haldane (Proc. R. Soc. Lond. 123, 119 (1937] measured the genetic distance between colour blindness and haemophilia. In their Discussion they wrote 'if...an equally close linkage were found between the genes determining blood group membership and that determining Huntington's chorea, we should be able, in many cases, to predict which children of an affected person would develop this disease, and to advise on the desirability or otherwise of their marriage'. Progress in this direction has proceeded through the discovery of autosomal linkages by family studies, and the assignment of genes to particular chromosomes by somatic-cell hybridization techniques. Recombinant DNA technology has been successfully used in both approaches, with the result that many chromosomes are now roughly mapped. In practice, the map can already be used for prenatal diagnosis of several diseases, and may provide 'take-off' points for some molecular approaches to poorly defined genes. More fundamentally, it is beginning to provide insights into the nature of the meiotic process and the organization of the genome.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos , Genes , Clonación Molecular , Ingeniería Genética , HumanosRESUMEN
The contribution of von Willebrand factor (vWF)-platelet binding to platelet-collagen interaction was examined in vitro. The binding of vWF to platelets was mediated and regulated by ristocetin. Subthreshold concentrations of ristocetin (less than or equal to 1 mg/mL), insufficient to cause ristocetin-induced platelet aggregation (RIPA), were added to platelet-rich plasma (PRP) prior to the addition of collagen. The collagen-induced platelet aggregation (CIPA) was modified by ristocetin and the degree of alteration was dependent on the ristocetin concentration. Response as a function of ristocetin concentration was designated the Collagen-Platelet Aggregation Response (CoI-PAR). In normal PRP the CoI-PAR was a progressive inhibition followed by decreasing inhibition and then an enhanced response. The enhanced response occurred over a narrow range of ristocetin concentrations (0.8 to 1.0 mg/mL). In the absence of vWF (severe von Willebrand's disease, Type I, vWF less than 1%) the CoI-PAR was a progressive, eventually complete inhibition with no enhanced response (with ristocetin concentrations up to 3.0 mg/mL). With addition of vWF to this PRP an enhanced response was observed at a ristocetin concentration inversely proportional to the vWF level. PRP from a patient with severe Hemophilia A showed a response within the normal range. Subthreshold ristocetin did not cause plasma protein precipitation or platelet release of 3H-serotonin, nor induce micro platelet aggregate formation. Digestion of platelet membrane glycoproteins (GP(s] with chymotrypsin demonstrated that upon removal of GPI, RIPA was absent, CIPA retained and the CoI-PAR was progressive inhibition, with no enhancement. With removal of GPs I, II, and III, RIPA, CIPA, and the CoI-PAR were absent. A dose-response 125I-vWF-platelet binding occurred with increasing ristocetin concentrations which was unchanged by the addition of collagen. These results demonstrated that ristocetin-platelet association inhibited CIPA, and vWF-platelet binding enhanced platelet-collagen adhesion and platelet aggregation. The in vitro-enhanced CIPA represents a vWF-dependent aggregation of sufficient magnitude to overcome the inhibitory effect of ristocetin. These studies demonstrate an influential interaction of ristocetin, vWF, and collagen with the platelet membrane and imply an important hemostatic contribution of vWF-platelet binding in platelet-collagen interaction.
Asunto(s)
Plaquetas/metabolismo , Colágeno/metabolismo , Ristocetina/farmacología , Factor de von Willebrand/metabolismo , Quimotripsina , Relación Dosis-Respuesta a Droga , Heparina/farmacología , Humanos , Agregación Plaquetaria/efectos de los fármacos , Glicoproteínas de Membrana Plaquetaria/fisiología , Unión Proteica , Serotonina/metabolismoRESUMEN
A large linkage group has been assigned to chromosome 19. The loci have been ordered using a two-point mapping analysis based on all available family linkage data summarized in the form of lod score tables.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos 19-20 , Ligamiento Genético , Femenino , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , Modelos Genéticos , Factores Sexuales , Estadística como AsuntoRESUMEN
Two common restriction fragment length polymorphisms detected with cloned gene probes for apolipoprotein CII (apo CII) have been used to study the inheritance of the gene in families segregating for loci on chromosome 19. Lod scores for APOC2 with the gene for complement component 3 (C3) exclude close linkage and give a maximum at a male recombination fraction of 0.25-0.30. Lod scores for APOC2 and FHC, the gene causing familial hypercholesterolaemia, are negative in males and suggest the genes may not be linked. However, it appears that APOC2 may be closely linked to the blood group loci Lutheran (Lu) and Secretor (Se), and probably less closely linked to Lewis (Le). These data are consistent with the gene order: FHC-----C3-----(Lu, Se, APOC2)
Asunto(s)
Apolipoproteínas C/genética , Mapeo Cromosómico , Cromosomas Humanos 19-20/ultraestructura , ADN Recombinante , Ligamiento Genético , Apolipoproteína C-II , Antígenos de Grupos Sanguíneos/genética , Complemento C3/genética , Femenino , Marcadores Genéticos , Humanos , Hiperlipoproteinemia Tipo II/genética , Masculino , Linaje , Polimorfismo GenéticoRESUMEN
Lod scores are presented from the published and unpublished data of the Galton Laboratory, and from published data on sixteen chromosome 1 loci, AMY, AT3, CAE, CMT1, EL1, ENO1, FUCA, Fy, GDH, PEPC, PGD, PGM1, Rh, Sc, UMPK and 1qh.
Asunto(s)
Cromosomas Humanos 1-3 , Familia , Ligamiento Genético , Escala de Lod , Mapeo Cromosómico , Femenino , Marcadores Genéticos , Humanos , Masculino , Recombinación Genética , Reino UnidoRESUMEN
The genetic map of chromosome 1 reported by Keats, Morton & Rao (1981) has been updated using recent recombination data and regional assignments from the Galton Laboratory (King, 1982a) and from the current literature. A maximum likelihood mapping technique using pairwise recombination data without a chiasma map was developed, based on the principles of Rao et al. (1979) and Keats et al. (1981). The development of this new method was found to be necessary when inconsistencies were encountered using a method which combines recombination data and physical data through the chiasma map. These inconsistencies could be due to appreciable chiasma movement, incorrect physical assignments or technical and biological variation in lod scores.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos 1-3 , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , Recombinación GenéticaRESUMEN
In a linkage study between myotonic dystrophy and peptidase D it is evident from the lod score values that with high probability theta lies between 0 and 0.1. The data thus support a previous hint of linkage between peptidase D and the Lutheran and secretor loci, which were already known to be linked to myotonic dystrophy.
Asunto(s)
Dipeptidasas/genética , Ligamiento Genético , Escala de Lod , Distrofia Miotónica/genética , Adulto , Factores de Edad , Mapeo Cromosómico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distrofia Miotónica/enzimología , Linaje , Recombinación GenéticaRESUMEN
A 69,XXX liveborn baby was shown to have the Rh genotype CDe/cDE/cde which suggested that 46 of her chromosomes were of paternal origin. Studies on C band polymorphisms and other genetic markers indicated that the most likely origin of this triploid was a failure of male meiosis II.
Asunto(s)
Anomalías Múltiples/genética , Aneuploidia , Enfermedades del Recién Nacido/genética , Antígenos de Grupos Sanguíneos/genética , Bandeo Cromosómico , Cromosomas Humanos/ultraestructura , Femenino , Marcadores Genéticos , Humanos , Recién Nacido , CariotipificaciónRESUMEN
A family with two nucleoside phosphorylase-deficient patients has been scored for the segregation of NP0 and the variable region 14p. The mose likely 14p:NP recombination fraction is 0.15 in males and 0.30 in females. There is no family data to assign the Pi:Gm linkage group to chromosome 14, but as immunoglobulin heavy chain has been assigned to this chromosome by somatic cell methods the most likely gene order is 14p:NP:Pi:Gm with Pi in 14q2 and Gm in 14(q23 leads to q32), but the order 14p:NP:Gm:Pi with Pi in 14(q24 leads to qter) and Gm in 14(q22 leads to q24) is not excluded. The available linkage data between biochemical markers on acrocentric chromosomes and their short arm markers suggest that there may be more recombination towards the ends of human chromosomes whether or not those ends carry centromeres.