RESUMO
The parental origin of the extra chromosome 21 was determined with DNA polymorphisms in seven families in whom the proband and one of the parents carried an additional chromosome rearrangement (balanced translocation or pericentric inversion) not involving chromosome 21. The balanced rearrangement was inherited from the mother in two families and from the father in five families, whereas the additional chromosome 21 was derived from the mother in all seven families. These findings are not in agreement with the hypothesis of a paternal interchromosomal effect. The latter would imply that a balanced rearrangement in the father would favor nondisjunction during meiosis in the germ cells.
Assuntos
Síndrome de Down/genética , Não Disjunção Genética , Adulto , Cromossomos Humanos Par 21 , DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Translocação GenéticaRESUMO
Down syndrome is rarely due to a de novo duplication of chromosome 21 [dup(21q)]. To investigate the origin of the dup(21q) and the nature of this chromosome, we used DNA polymorphisms in 10 families with Down syndrome due to de novo dup(21q). The origin of the extra chromosome 21q was maternal in six cases and paternal in four cases. Furthermore, the majority (eight of 10) of dup(21q) chromosomes were isochromosomes i(21q) (four were paternal in origin, and four were maternal in origin); however, in two of 10 families the dup(21q) chromosome appeared to be the result of a Robertsonian translocation t(21q;21q) (maternal in origin in both cases).
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 21 , Síndrome de Down/genética , Polimorfismo de Fragmento de Restrição , Translocação Genética , Pai , Feminino , Humanos , MasculinoRESUMO
Down syndrome is rarely due to a de novo Robertsonian translocation t(14q;21q). DNA polymorphisms in eight families with Down syndrome due to de novo t(14q;21q) demonstrated maternal origin of the extra chromosome 21q in all cases. In seven nonmosaic cases the DNA markers showed crossing-over between two maternal chromosomes 21, and in one mosaic case no crossing-over was observed (this case was probably due to an early postzygotic nondisjunction). In the majority of cases (five of six informative families) the proximal marker D21S120 was reduced to homozygosity in the offspring with trisomy 21. The data can be best explained by chromatid translocation in meiosis I and by normal crossover and segregation in meiosis I and meiosis II.
Assuntos
Cromossomos Humanos Par 14 , Cromossomos Humanos Par 21 , Síndrome de Down/genética , Translocação Genética/genética , Adulto , Troca Genética/genética , Feminino , Humanos , Masculino , Idade Materna , Meiose/genética , Polimorfismo Genético/genéticaRESUMO
Uniparental disomy has been recently recognized as an important phenomenon in non-Mendelian inheritance of human genetic disorders. Several mechanisms for uniparental disomy, i.e., the presence of two homologous chromosomes derived from one parent, have been proposed. We studied two independent cases of abnormalities of chromosome 21 in which there were abnormal karyotypes at birth but blood cells with normal karyotype predominated later in life, and the cells with abnormalities disappeared. Uniparental isodisomy was observed in the normal cells in these individuals. The uniparental disomy in these families was the result of duplication of a chromosome in mitosis after the loss of the homologous abnormal chromosome. The duplication can be seen as mechanism for cell survival and is called here "compensatory" isodisomy, which provided a selective advantage for the cell population with the normal number of chromosomes 21.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas/genética , Cromossomos Humanos Par 21 , Deficiência Intelectual/genética , Monossomia , Mosaicismo , Não Disjunção Genética , Deleção Cromossômica , Transtornos Cromossômicos , Feminino , Retardo do Crescimento Fetal/genética , Transtornos do Crescimento/genética , Humanos , Recém-Nascido , Modelos Genéticos , Polimorfismo de Fragmento de RestriçãoRESUMO
The origin of meiotic nondisjunction of the extra chromosomes X and 21 was studied in a patient with the karyotype 48,XXY,+21 using DNA polymorphisms. The extra chromosome X was the result of paternal first meiotic nondisjunction of X and Y. The extra chromosome 21 was derived from the mother. The meiotic error in the mother most probably occurred in meiosis II. Thus, this is a combination caused by the chance occurrence of two independent events.
Assuntos
Cromossomos Humanos Par 21 , Síndrome de Down/genética , Síndrome de Klinefelter/genética , Cromossomo X , Aneuploidia , Autorradiografia , Southern Blotting , Humanos , Recém-Nascido , Masculino , Polimorfismo de Fragmento de RestriçãoRESUMO
We have studied DNA polymorphisms at loci in the pericentromeric region on the long arm of chromosome 21 in 200 families with trisomy 21, in order to determine the meiotic origin of nondisjunction. Maintenance of heterozygosity for parental markers in the individual with trisomy 21 was interpreted as resulting from a meiosis I error, while reduction to homozygosity was attributed to a meiosis II error. Nondisjunction was paternal in 9 cases and was maternal in 188 cases, as reported earlier. Among the 188 maternal cases, nondisjunction occurred in meiosis I in 128 cases and in meiosis II in 38 cases; in 22 cases the DNA markers used were uninformative. Therefore meiosis I was responsible for 77.1% and meiosis II for 22.9% of maternal nondisjunction. Among the 9 paternal nondisjunction cases the error occurred in meiosis I in 2 cases (22.2%) and in meiosis II in 7 (77.8%) cases. Since there was no significant difference in the distribution of maternal ages between maternal I error versus maternal II error, it is unlikely that an error at a particular of maternal ages between maternal I error versus maternal II error, it is unlikely that an error at a particular meiotic stage contributes significantly to the increasing incidence of Down syndrome with advancing maternal age. Although the DNA polymorphisms used were at loci which map close to the centromere, it is likely that rare errors in meiotic-origin assignments may have occurred because of a small number of crossovers between the markers and the centromere.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cromossomos Humanos Par 21 , Síndrome de Down/genética , Meiose/genética , Não Disjunção Genética , Polimorfismo Genético/genética , Adulto , Centrômero , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Mapeamento Cromossômico , Troca Genética/genética , DNA/genética , Feminino , Ligação Genética/genética , Marcadores Genéticos , Humanos , Masculino , Idade Materna , Idade Paterna , Polimorfismo de Fragmento de RestriçãoRESUMO
We used DNA polymorphic markers on the long arm of human chromosome 21 in order to determine the parental and meiotic origin of the extra chromosome 21 in families with recurrent free trisomy 21. A total of 22 families were studied, 13 in which the individuals with trisomy 21 were siblings (category 1), four families in which the individuals with trisomy 21 were second-degree relatives (category 2), and five families in which the individuals with trisomy 21 were third-degree relatives, that is, their parents were siblings (category 3). In five category 1 families, parental mosaicism was detected, while in the remaining eight families, the origin of nondisjunction was maternal. In two of the four families of category 2 the nondisjunctions originated in individuals who were related. In only one of five category 3 families, the nondisjunctions originated in related individuals. These results suggest that parental mosaicism is an important etiologic factor in recurrent free trisomy 21 (5 of 22 families) and that chance alone can explain the recurrent trisomy 21 in many of the remaining families (14 of 22 families). However, in a small number of families (3 of 22), a familial predisposing factor or undetected mosaicism cannot be excluded.