RESUMEN
The effect of random red cell transfusions given shortly before allogeneic bone marrow transplantation (BMT) was evaluated in 969 leukemic patients transplanted from an HLA-identical sibling donor. Patients were divided into two groups: 501 who received a transfusion shortly before BMT, and 468 who did not. Both groups had a similar incidence of acute graft-versus-host disease (GVHD), but the recently-transfused group had a significantly lower incidence of chronic GVHD (35.9% vs 48.9%). These differences remained significant in a multivariate analysis of time to chronic GVHD (p = 0.022), taking into account other differences between the two groups and known risk factors for chronic GVHD.
Asunto(s)
Transfusión Sanguínea , Trasplante de Médula Ósea/métodos , Refuerzo Inmunológico de Injertos , Enfermedad Injerto contra Huésped/prevención & control , Leucemia/cirugía , Adulto , Trasplante de Médula Ósea/efectos adversos , Enfermedad Crónica , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Histocompatibilidad , Humanos , Incidencia , Estudios Retrospectivos , Washingtón/epidemiologíaRESUMEN
Blood samples from a random series of Canadian Caucasians were phenotyped for 28 red cell enzyme systems and eight plasma protein systems. Polymorphism was found in 17 and rare variants in 11 of the systems. Allele frequencies are presented for these; distribution of phenotypes is in accordance with the Hardy--Weinberg equilibrium theory. In a complementary study of families there was no evidence of de novo mutation in any of the 36 systems and they allowed a minimum estimate of the frequency of null alleles in the ADA, C2, and GPT systems.
Asunto(s)
Proteínas Sanguíneas/genética , Enzimas/genética , Eritrocitos/enzimología , Polimorfismo Genético , Alelos , Proteínas Sanguíneas/aislamiento & purificación , Canadá , Niño , Enzimas/sangre , Femenino , Frecuencia de los Genes , Ligamiento Genético , Humanos , Masculino , Fenotipo , Población BlancaRESUMEN
Allele frequencies of Yta (YT1) and Ytb (YT2) in a series of 659 random Canadian Caucasians are comparable to those in European populations: 0.9469 and 0.0531, respectively. Inheritance of Yt phenotypes in 1,077 children in 286 selected families are in accordance with expectation on the basis of Mendelian codominance. Linkage studies exclude YT from chromosomal segments 1p36-1p22.1, 4q13-4q28, the section of chromosome 9 bounded by AB0 and AK1 and from the chromosome 19 linkage group bounded by LE and SE. Evidence is presented for a possible location of YT on the short arm of chromosome 6 distal to F13A.
Asunto(s)
Antígenos de Grupos Sanguíneos/genética , Mapeo Cromosómico , Ligamiento Genético , Marcadores Genéticos , Humanos , FenotipoRESUMEN
The frequencies of HLA-A, B, C, DR, and DQ antigens, HLA-D (HTC-defined) haplotypes, and the HLA-linked genetic markers glyoxalase I (GLO), factor B (Bf), C2 and C4 were studied in 162 healthy unrelated Koreans. Antigens A2, A24, A26, B44, B51, Bw62, B35, Cw1, Cw3, DR2, DR4, DRw6, DR7, and DRw8 were observed at frequencies of 15% or greater, and GLO-2, BfS, C4A*3, C2C, C4A*4, C4B*1, and C4B*2 were also frequently observed. The antigens A23, A25, B18, Bw42, Bw47, and B21 were not observed at all. HLA-DR4 was the most common class II antigen and was associated with a series of HLA-D-defined haplotypes including Dw4, Dw10, Dw13, and Dw15. The HLA-DRw6, DR2,Dw8, and DRw8 haplotypes were also found frequently. DR2 haplotypes were either Dw2 or Dw12, while all DRw8 haplotypes tested corresponded to the DB7 or Dw "8.3" specificity that has been described in other Oriental populations. Significant linkage disequilibrium was found between the alleles A2,Cw1; A30,B13; A30,Cw6; A30,DR7; Cw1,Bw22; Cw5,B12; Cw6,B13; Cw6,DR7; B7,DR1; B12,Dw6; B12,DR7; B12,Dw7; B13,DR7, B17,DR3; Bw22,C4B*6; DRw6,BfF; and C4A*4,C4B*2. A comparison of gene frequencies and commonly observed haplotypes between Koreans, Chinese, Japanese, and Caucasians showed that while Koreans share several characteristics in common with other Oriental populations, there are allelic frequencies and haplotypes in Koreans that are distinct.
Asunto(s)
Antígenos HLA/genética , Complemento C2/genética , Complemento C4/genética , Frecuencia de los Genes , Pruebas Genéticas , Antígenos HLA-D/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Humanos , Corea (Geográfico) , Lactoilglutatión Liasa/genéticaRESUMEN
Cytogenetic, enzyme dosage, serological, and electrophoretic analyses of blood samples from members of three Newfoundland kindreds in which one specific paracentric insertion chromosome inv ins(9)(q22.1q34.3q34.1) is segregating provide data indicating that ABO lies in 9q22.1-q34.3, AK1 in 9q34.1-q34.3, and ORM in 9q34.3-qter.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/genética , Adenilato Quinasa/genética , Aberraciones Cromosómicas/genética , Cromosomas Humanos Par 9/ultraestructura , Orosomucoide/genética , Fosfotransferasas/genética , Deleción Cromosómica , Trastornos de los Cromosomas , Mapeo Cromosómico , Intercambio Genético , Marcadores Genéticos , Humanos , LinajeRESUMEN
Ninety-eight alleles in 38 polymorphisms of blood are identified in the Schmiedeleut Hutterites. The study was initiated because of the presence of Wda, an allele found almost exclusively in Hutterites. Eight of the other alleles also have an exceedingly low incidence in a random white population: r'' (.006), R2w (less than .001), LWb (less than .01), ESD*rare (less than .001), GPT*0 (.004), NP*4 (less than .001), GOT2*3 (.001), and C6*0 (.002). The occurrence of this many rare alleles in a population with an estimated maximum of 124 ancestral genomes was surprising but consistent with observations in other isolates. The degree of heterozygosity and large family size make the population ideal for genetic linkage studies.
Asunto(s)
Antígenos de Grupos Sanguíneos/genética , Proteínas Sanguíneas/genética , Genética de Población , Eritrocitos/enzimología , Frecuencia de los Genes , Ligamiento Genético , Humanos , Leucocitos/enzimología , Manitoba , Linaje , Polimorfismo GenéticoAsunto(s)
Adenosina Desaminasa/deficiencia , Síndromes de Inmunodeficiencia/genética , Nucleósido Desaminasas/deficiencia , Pentosiltransferasa/deficiencia , Purina-Nucleósido Fosforilasa/deficiencia , Síndrome de Inmunodeficiencia Adquirida/enzimología , Síndrome de Inmunodeficiencia Adquirida/genética , Adenosina Desaminasa/metabolismo , Inhibidores de la Adenosina Desaminasa , Animales , Transfusión Sanguínea , Trasplante de Médula Ósea , Humanos , Síndromes de Inmunodeficiencia/enzimología , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/terapia , Ratones , Purina-Nucleósido Fosforilasa/antagonistas & inhibidores , Purina-Nucleósido Fosforilasa/metabolismo , Linfocitos T/inmunologíaRESUMEN
A genetic linkage study performed on a large family with autosomal dominant Charcot-Marie-Tooth neuropathy (HMSN type I) showed affected family members to have slow motor nerve conduction velocities, hypoactive tendon reflexes, and distal muscle weakness and atrophy. Results excluded close linkage of the neuropathy in this family to the Duffy blood group locus on chromosome 1. Previous studies in other families have shown positive linkage of HMSN type I to the Duffy locus. The present results provide support for the concept of genetic heterogeneity in HMSN type I. Comparison of this new family with the previous families showing linkage to Duffy reveals that the hereditary neuropathy not linked to the Duffy locus may have less severe slowing of motor nerve conduction velocities and less prominent onion bulb change evident on sural nerve biopsy.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Ligamiento Genético , Atrofia Muscular/genética , Adolescente , Adulto , Anciano , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Niño , Cromosomas Humanos 1-3 , Sistema del Grupo Sanguíneo Duffy/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas Motoras/fisiopatología , Conducción NerviosaRESUMEN
Plasma paraoxonase hydrolyzes paraoxon, the principal metabolite of the insecticide parathione. A genetic polymorphism for enzyme activity has been previously demonstrated. We describe a new assay based on the differential inhibition by EDTA of plasma paraoxonase from persons with the high-activity allele (PX*H) that suggests a trimodality of activity levels in population studies. The gene frequency of the low activity allele (PX*L) in 531 Seattle blood donors of European origin was .7207. Family studies were consistent with codominant autosomal inheritance of two alleles, PX*L (low) and PX*H (high), coding for products with different activity levels. Biochemical measurements of sera from presumed homozygotes for the two different alleles revealed minor physicochemical differences suggestive of a structural difference between the allelic products. No evidence for linkage of the paraoxonase locus with any of 19 polymorphic markers would be detected.
Asunto(s)
Monoéster Fosfórico Hidrolasas/genética , Polimorfismo Genético , Adolescente , Adulto , Factores de Edad , Anciano , Alelos , Arildialquilfosfatasa , Niño , Preescolar , Ácido Edético/metabolismo , Femenino , Frecuencia de los Genes , Calor , Humanos , Concentración de Iones de Hidrógeno , Lactante , Cinética , Masculino , Persona de Mediana Edad , Monoéster Fosfórico Hidrolasas/metabolismo , Factores SexualesRESUMEN
Isoelectric focusing was used to identify five alleles at the locus determining the production of the sixth component of complement (C6) in the dog. Four of these alleles, C6(1), C6(2), C6(4), and C6(5), were studied in family pedigrees and shown to be inherited in a codominant autosomal fashion. All alleles except for C6(4) occurred commonly in the multiple breeds tested.
Asunto(s)
Complemento C6/genética , Genes Dominantes , Genes , Polimorfismo Genético , Alelos , Animales , Perros , Femenino , Masculino , LinajeRESUMEN
One hundred seventy-five patients with severe aplastic anemia were treated by high-dose cyclophosphamide and HLA-A, -B, and -D-identical sibling marrow transplants. Thirty-eight patients rejected their grafts. Four of the 38 showed autologous marrow recovery as determined by blood genetic markers. The remarkable feature of one case following autologous marrow recovery was the presence of unidirectional proliferative and cytotoxic responses of circulating host lymphocytes to marrow donor lymphocytes in mixed lymphocyte culture and cell-mediated lympholysis. Presumably these responses were the result of in vivo sensitization to those non-HLA antigens for which donor and recipient differed.
Asunto(s)
Anemia Aplásica/terapia , Trasplante de Médula Ósea , Antígenos HLA/genética , Inmunización , Adolescente , Adulto , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/inmunología , Médula Ósea/inmunología , Células de la Médula Ósea , Niño , Ciclofosfamida/uso terapéutico , Pruebas Inmunológicas de Citotoxicidad , Sistema del Grupo Sanguíneo Duffy , Femenino , Rechazo de Injerto/efectos de los fármacos , Humanos , Prueba de Cultivo Mixto de Linfocitos , MasculinoRESUMEN
Alanine aminotransferase (ALT) phenotype and serum activities were determined in 200 random volunteer blood donors. Serum enzyme activities were not significantly affected by the ALT phenotype (p greater than 0.1). Studies on 500 random volunteer blood donors showed significant differences in serum ALT levels between male and female donors (p less than 0.001). Elevated serum ALT levels were more commonly found in male donors; the frequency of male donors with levels of 45 IU/l or higher was 2.5 percent compared with 0.9 percent in female donors. The frequency of donors with serum ALT levels of 80 IU/l or higher was 0.6 percent of the total donor population sampled.
Asunto(s)
Alanina Transaminasa/sangre , Donantes de Sangre , Alanina Transaminasa/genética , Transfusión Sanguínea , Femenino , Hepatitis C/prevención & control , Humanos , Masculino , Fenotipo , Factores SexualesRESUMEN
A linkage study was performed on three families with classic Charcot-Marie-Tooth (CMT) hereditary neuropathy with clinical manifestations of autosomal dominant inheritance, distal muscle weakness and atrophy, hyporeflexia, and slow motor nerve conduction velocities. Two families comprising 3 and 4 generations and a total of 23 affected persons were informative for the Duffy locus known to be on the long arm of chromosome 1. The maximum total lod score was 2.297 at recombination fraction theta = .1. The third family was informative for PGM1 (on the short arm of chromosome 1). There was no evidence for linkage of CMT to PGM1 in this third family, but only values of theta less than .03 could be excluded. There was no evidence for linkage of CMT to seven other informative markers in these families. We conclude that the gene controlling the occurrence of dominant CMT may be approximately 10 centimorgans from the Duffy locus on the long arm of chromosome 1. Additional studies are required to confirm these findings.
Asunto(s)
Antígenos de Grupos Sanguíneos/genética , Enfermedad de Charcot-Marie-Tooth/genética , Mapeo Cromosómico , Cromosomas Humanos 1-3 , Sistema del Grupo Sanguíneo Duffy/genética , Atrofia Muscular/genética , Femenino , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , LinajeRESUMEN
We have compared phenotypic markers for a series of established human leukemic T-cell lines collected from different laboratories. Cell lines were tested first for genetic markers using polymorphic enzymes and then for expression of T lymphoid cell surface differentiation antigens using monoclonal antibodies. Chromosomal analysis was used as an additional method for identification of selected cell lines. On the basis of enzyme markers, it was possible to assign each of the cell lines examined to one of nine different groups. With two exceptions, surface antigen phenotypes for each of 12 cell lines were clearly distinctive. Thus, some groups of cell lines indistinguishable by enzyme markers could be further subdivided by surface antigen phenotyping. However, significant quantitative variation in expression of individual antigens was observed. In addition, surface antigen expression was not uniform in different subcultures of one cell line studied in detail. These results indicate that leukemic T-cell lines cannot be used generally as simple models of surface antigen expression in normal T-cell differentiation.
Asunto(s)
Antígenos de Superficie/inmunología , Marcadores Genéticos , Leucemia Linfoide/inmunología , Linfocitos T/inmunología , Anticuerpos Monoclonales/inmunología , Línea Celular , Femenino , Humanos , Leucemia Linfoide/genética , Masculino , FenotipoAsunto(s)
Síndromes de Inmunodeficiencia/etiología , Linfocitos/enzimología , Adenosina Desaminasa/deficiencia , Adenosina Desaminasa/genética , Transfusión de Eritrocitos , Humanos , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/terapia , Transfusión de Linfocitos , Nucleotidasas/deficiencia , Purina-Nucleósido Fosforilasa/deficiencia , Purina-Nucleósido Fosforilasa/genéticaRESUMEN
We have studied nine families in which at least one member has congenital adrenal hyperplasia, to compare the predictive value of HLA typing and the 17-hydroxy progesterone response to ACTH as methods for detection of heterozygotes. In each of six families, two children were affected and were HLA genotypically identical. None of the unaffected siblings were HLA identical with their affected siblings. When the 17-OHP response to ACTH and the HLA haplotypes of parents and unaffected siblings were compared, there was a 79% concordance for identification of heterozygotes. Two siblings were carriers according to HLA typing, but had normal 17-OHP responses consistent with the carrier state. Three individuals with recombinations involving the HLA region of chromosome number 6 were detected. Analysis of these recombinant individuals provided additional evidence suggesting that the 21-OH degrees gene is closely associated with the B-locus of HLA. When an affected individual has been identified, HLA typing is a direct and reliable method for determining the carrier state among family members.