RESUMO
Linkage is reported between the expressed hypervariable gene locus PUM and the gene coding for the Duffy blood group FY, with a maximum lod score of 4 at theta = 0. Linkage can be excluded between PUM and PEPC at a distance of 10 cM.
Assuntos
Antígenos de Grupos Sanguíneos/genética , Sistema do Grupo Sanguíneo Duffy/genética , Genes de Imunoglobulinas , Ligação Genética , Região Variável de Imunoglobulina/genética , Lectinas/genética , Mucinas/genética , Genes , Humanos , Escore Lod , Aglutinina de AmendoimRESUMO
Deficiency of alpha 1 antitrypsin (Pi) is clinically heterogeneous and the unpredictability of the clinical manifestation in a person of phenotype PiZ, which may vary from severe childhood liver disease to normal health, is a problem in genetic counselling. This problem may increase as couples at risk who have not had an affected child are identified in screening programmes. One possibility is that genetic variation of other protease inhibitors may influence the prognosis. With this in mind we report the isolation of the human gene for alpha 1 antichymotrypsin (AACT) on a series of cosmid clones, with restriction mapping of about 70 kb around the gene. A probe pACE3.4 derived from the 5' end of the gene defines sequences which have been assigned to chromosome 14 using somatic cell hybrids and has been used to show a common TaqI polymorphism with allele frequencies of AACT6 = 0.7 and AACT3 = 0.3 in Europeans. pACE3.4 is closely linked to alpha 1 antitrypsin (maximum lod score in males +2.29 at theta = 0; in females Z = +6.11 at theta = 0.032). Analysis of Pi-AACT haplotypes in 31 families ascertained through PiZ or PiSZ subjects did not show any linkage disequilibrium. The distribution of AACT6 and AACT3 alleles in 16 unrelated PiZ patients presenting with childhood liver disease and five unrelated PiZ patients with adult chest disease did not differ significantly from each other. These results suggest that if genetic variation at the AACT locus does influence the outcome of alpha 1 antitrypsin deficiency, such variation is not in linkage disequilibrium with the AACT polymorphism reported here.
Assuntos
Clonagem Molecular , Genes , alfa 1-Antiquimotripsina/genética , Deficiência de alfa 1-Antitripsina , Feminino , Genótipo , Humanos , Escore Lod , Masculino , Fenótipo , alfa 1-Antitripsina/genéticaRESUMO
Adult polycystic kidney disease (APKD) is a common genetic disorder that is inherited as an autosomal dominant trait. Recent reports show that, in some families, the APKD gene shows close genetic linkage to two chromosome 16 specific genetic markers. We have been conducting a genetic linkage study using 29 polymorphic isoenzyme and antigenic markers in 184 members of 12 APKD families. We present here the results of linkage analysis using three of these markers which have also been reported to be located on chromosome 16: phosphoglycolate phosphatase (PGP), glutamate pyruvate transaminase (GPT), and haptoglobin (HP). The results show that APKD is closely linked to the PGP locus on the short arm of chromosome 16 (16p13----p12), which is consistent with the previously reported linkage both to PGP and to the alpha globin locus. The genetic distance between PGP and APKD shows a maximum likelihood value of the recombination fraction at zero with a lod score of 5 X 5. There is no evidence of linkage between APKD and either GPT or HP. The PGP polymorphism potentially provides a useful predictive test to complement the use of alpha globin probes in genetic counselling. These tests should provide an efficient means of primary screening of family members at risk, as well as introducing the possibility of prenatal diagnosis.
Assuntos
Alanina Transaminase/genética , Cromossomos Humanos Par 16 , Ligação Genética , Haptoglobinas/genética , Monoéster Fosfórico Hidrolases/genética , Doenças Renais Policísticas/genética , Feminino , Genes Dominantes , Marcadores Genéticos , Humanos , Masculino , Linhagem , Polimorfismo GenéticoRESUMO
A single highly-polymorphic autosomal gene locus PUM codes for a family of mucin-type glycoproteins, separable by SDS-gel electrophoresis, which we first identified in human urine. The locus also codes for glycoproteins which are abundant in several other normal epithelial tissues and body fluids, including milk, and in tumours of epithelial origin. These mucin-type glycoproteins seem to be very immunogenic in rodents and, in a search for epithelial specific or tumour-associated antigens, a large number of related antibodies have been isolated which bind to the PUM-coded mucins. Many of the antibodies show a pronounced tumour specificity on immunohistology and are being used widely in cancer diagnosis in vitro and in vivo and even in cancer therapy. To investigate the expression of these antigens in normal and malignant cells complementary DNA coding for the mammary mucin has been isolated. Here we present evidence obtained using this cDNA that the PUM locus is a hypervariable 'minisatellite' region of human DNA similar to those described by several groups, but which is novel in that it is transcribed and translated, and that the same polymorphism is demonstrable in the expressed gene product.
Assuntos
Lectinas/genética , Mucinas/genética , Polimorfismo Genético , Sequência de Bases , DNA/genética , DNA Recombinante , Epitélio/análise , Humanos , Mucinas/urina , Neoplasias/análise , Sequências Repetitivas de Ácido NucleicoRESUMO
Fetal blood sampling for the diagnosis of alpha-1-antitrypsin deficiency using protein isoelectric focusing was carried out in the period 1980-1985. The results of 25 cases from 18 mothers are reported. All had a previous history of a PiZ child affected by liver disease. The method was found to be technically satisfactory and the fetal results were subsequently confirmed in all 18 cases where follow-up was possible. The fetus was found to be PiZ in nine cases and all these pregnancies were terminated. Of the remaining pregnancies three cases aborted or were delivered prematurely and 13 proceeded to term without complications.
Assuntos
Sangue Fetal/enzimologia , Diagnóstico Pré-Natal , Deficiência de alfa 1-Antitripsina , Adulto , Eletroforese das Proteínas Sanguíneas , Feminino , Doenças Fetais/diagnóstico , Idade Gestacional , Humanos , Hepatopatias/diagnóstico , Fenótipo , GravidezRESUMO
The genetic locus for autosomal dominant adult polycystic kidney disease was recently assigned to chromosome 16 by the finding of genetic linkage to the alpha globin gene cluster. Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster. These findings have important implications for the prenatal and presymptomatic diagnosis of adult polycystic kidney disease and for a better understanding of its pathogenesis.
Assuntos
Cromossomos Humanos 16-18 , Globinas/genética , Doenças Renais Policísticas/genética , Adolescente , Adulto , Ligação Genética , Humanos , Linhagem , Monoéster Fosfórico Hidrolases/genética , Doenças Renais Policísticas/enzimologiaRESUMO
Families segregating for PEPD were investigated for linkage between PEPD and APOC2. The results provide evidence for close linkage between PEPD and APOC2 in males.
Assuntos
Apolipoproteínas C/genética , Mapeamento Cromossômico , Cromossomos Humanos 19-20 , Dipeptidases/genética , Ligação Genética , Apolipoproteína C-II , Enzimas de Restrição do DNA , Feminino , Humanos , Escore Lod , Masculino , LinhagemRESUMO
A preliminary analysis of twins or triplets with heart defects, ascertained in five centres, confirms earlier suggestions that monozygotic (MZ) twins are over represented among twins with heart defects, even after excluding persistent ductus arteriosus and conjoined twins. An MZ twin individual has a risk of cardiovascular malformation approximately twice that of DZ twins and singletons. It is suggested that the twinning process itself affects one of the pair. Disturbance of laterality ('mirror imaging') is probably a more important mechanism than twin-twin transfusion. Inappropriate use of the twin method in the past has caused the importance of genetic factors in the etiology of congenital heart defects to be underestimated. Nevertheless, twins do provide a useful illustration of the likely importance of epigenetic factors in heart development.
Assuntos
Doenças em Gêmeos , Cardiopatias Congênitas/genética , Feminino , Lateralidade Funcional , Humanos , Masculino , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Trigêmeos , Gêmeos MonozigóticosAssuntos
Gêmeos , Inglaterra , Feminino , Genética/história , História do Século XIX , História do Século XX , Humanos , GravidezRESUMO
We report here a novel genetically determined polymorphism of a human urinary mucin which is demonstrable by the separation technique of SDS polyacrylamide gel electrophoresis, followed by detection with radio-iodinated lectins. The mucins are demonstrable using various lectins but the polymorphism is most easily recognized using peanut agglutinin and we therefore propose to designate this new genetic locus PUM (peanut-reactive urinary mucin). Four common alleles have been identified and an autosomal codominant mode of inheritance has been found in the families studied so far.
Assuntos
Mucinas/genética , Polimorfismo Genético , Alelos , Antígenos de Grupos Sanguíneos/genética , Mapeamento Cromossômico , Eletroforese em Gel de Poliacrilamida , Glicoproteínas/urina , Humanos , Lectinas , Mucinas/urina , Aglutinina de Amendoim , Fenótipo , Distribuição TecidualRESUMO
Data with regard to the proportion of congenital malformations found at birth are presented from a survey of 657 pairs of twins of known zygosity and placentation delivered in Aberdeen and Northeast Scotland between 1968 and 1979. There was an excess of malformed individuals from monozygotic (MZ) pairs, but this did not reach statistical significance. The possible effect of monochorionic placentation in the causation of malformations in MZ twins in general is discussed. It seems that this type of placentation may be of less causative importance than has been previously suggested.
Assuntos
Anormalidades Congênitas/genética , Doenças em Gêmeos , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Gêmeos , Anormalidades Congênitas/epidemiologia , Feminino , Humanos , Masculino , Placentação , Gravidez , EscóciaRESUMO
Data from six primary hybrids and twenty-two subclones have confirmed the assignment of the mitochondrial form of glutamate oxaloacetate transaminase to chromosome 16. Family studies have provided independent confirmation of this and have suggested the gene order PGP-16qh-GOT2-HP. These studies were made easier by the development of a new stain for the detection of GOT activity.
Assuntos
Aspartato Aminotransferases/genética , Cromossomos Humanos 16-18 , Animais , Aspartato Aminotransferases/metabolismo , Eletroforese em Gel de Amido , Humanos , Células Híbridas/enzimologia , Isoenzimas/genética , Isoenzimas/metabolismo , Escore Lod , Camundongos , Mitocôndrias/enzimologia , Linhagem , RatosRESUMO
Fibroblast cultures from six unrelated Huntington's Disease (HD) patients and controls and one affected relative of an HD patient were used in studies of cell growth, DNA repair, sister chromatid exchange (SCE) and chromosome aberrations. There were no significant differences in background levels of SCEs or of chromosome aberrations between HD cultures and controls. Preliminary results using epidermal growth factor indicated that HD cells may have a lowered relative response to this polypeptide hormone. Cell growth studies showed no correlation between growth rate and HD. Increased cell saturation density was recorded in cell lines from four of the HD patients; the remaining three lines from affected individuals (two of them related) were indistinguishable from control cultures. This variation may reflect genetic heterogeneity in HD. An apparent deficiency in DNA repair capacity following UV irradiation in cultures from three HD patients was subsequently shown to be the result of the increased cell saturation densities in these cultures.
Assuntos
Aberrações Cromossômicas , Troca Genética , Reparo do DNA , Doença de Huntington/genética , Troca de Cromátide Irmã , Adulto , Divisão Celular , Células Cultivadas , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/ultraestrutura , Glucosamina/metabolismo , Substâncias de Crescimento/farmacologia , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Gravidez Múltipla , Peso ao Nascer , Estatura , Doenças em Gêmeos , Feminino , Humanos , Síndrome de Klinefelter/etiologia , Masculino , Idade Materna , Menopausa , Paridade , Poli-Hidrâmnios/etiologia , Pré-Eclâmpsia/etiologia , Gravidez , Complicações na Gravidez/etiologia , Complicações na Gravidez/mortalidade , Fatores de Tempo , Síndrome de Turner/etiologia , Gêmeos Dizigóticos , Gêmeos MonozigóticosRESUMO
Linkage between the Scianna blood group and the Rhesus blood group has been confirmed. Families demonstrating recombinants between U M P K and Sc suggest that U M P K lies between Sc and PGM1.
Assuntos
Antígenos de Grupos Sanguíneos/genética , Cromossomos Humanos 1-3 , Núcleosídeo-Fosfato Quinase/genética , Fosfotransferases/genética , Mapeamento Cromossômico , Feminino , Ligação Genética , Humanos , Masculino , Recombinação Genética , Sistema do Grupo Sanguíneo Rh-Hr/genética , Uridina MonofosfatoRESUMO
Data on maternal height are presented for 307 pairs of newborn twins of known zygosity from Oxford and 267 pairs from Aberdeen and north-east Scotland. The results support the hypothesis that mothers of DZ twins are taller than those of MZ twins. Mothers of MZ twins resemble mothers of singletons in height, whereas mothers of DZ twins are taller.
Assuntos
Estatura , Gravidez Múltipla , Inglaterra , Feminino , Humanos , Gravidez , Escócia , Gêmeos Dizigóticos , Gêmeos MonozigóticosRESUMO
Birth weight data for 356 pairs of newborn twins of known zygosity and placentation are presented. The combined weights of dizygotic twins are heavier than those of monozygotic twins. The significance of this finding is discussed in relation to the association between increased maternal height and dizygotic twinning.
Assuntos
Peso ao Nascer , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Gêmeos , Estatura , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Idade Materna , Paridade , Gravidez , Escócia , Fatores SexuaisRESUMO
Family studies show that alphaFUC is closely linked to Rh and confirm that the locus for alpha-L-fucosidase is on chromosome 1.
