Parental origin of chromosomes in Down's syndrome

Summary The number of 21 chromosomes of 15 individuals with Down's syndrome and their parents were examined in an attempt to determine the parental origin of the extra number 21 chromosome and the stage of meiosis at which nondisjunction occurred. Chromosomes were stained with quinacrine hydrochloride and photographed; serial prints were made ranging from underexposed to overexposed. Twelve of the 15 families (80%) were informative: nondisjunction occurred in maternal meiosis I in eight (66.7%) families, in paternal meiosis I in two (16.7%) families, and in paternal meiosis II in two (16.7%) families. The production of serial exposures of chromosomes at the time of printing proved to be a valuable method of enhancing slight differences in short arm and satellite structure of the number 21 chromosomes and thereby increasing the number of informative families.     

Parental origin of the extra chromosome in trisomy 18.

The parental origin of the supernumerary chromosome 18 was investigated by RFLP analysis in 23 individuals with Edwards syndrome. All families were studied with the DNA probe pERT-25, which recognizes a locus of highly polymorphic tandemly repeated DNA sequences on chromosome 18. The extra chromosome was found to be of maternal origin in 19 patients (95%), of paternal origin in one patient (5%), and indeterminate in three patients. In one of the three indeterminate cases, a mosaic, an apparent recombination event had taken place within the pERT-25 locus. The overall high degree of informativeness of pERT-25 illustrates the power of a chromosome-specific variable-number tandem repeat probe (VNTR) in parental origin studies of aneuploidy.     

Origin of the extra chromosome No. 21 in Down's syndrome

Summary A No. 15 chromosome with a short arm longer than usual is observed in two phenotypically normal brothers. This chromosome appears to have no visible satellite, shows no N-band staining, and is never involved in satellite association. These results have led us to the conclusion that this chromosome lacks the nucleolus organizer region.     

Parental origin of the extra chromosome in prenatally diagnosed fetal trisomy 21

Trisomy 21 (Down syndrome) is one of the most common chromosomal abnormalities. Of cases of free trisomy 21 causing Down syndrome, about 95% result from nondisjunction during meiosis, and about 5% are due to mitotic errors in somatic cells. Previous studies using DNA polymorphisms of chromosome 21 showed that paternal origin of trisomy 21 occurred in only 6.7% of cases. However, these studies were conducted in liveborn trisomy 21-affected infants, and the possible impact of fetal death was not taken into account. Using nine distinct DNA polymorphisms, we tested 110 families with a prenatally diagnosed trisomy 21 fetus. Of the 102 informative cases, parental origin was maternal in 91 cases (89.2%) and paternal in 11 (10.8%). This percentage differs significantly from the 7.0% observed in previous studies (P<0.001). In order to test the influence of genomic parental imprinting, we determined the origin of the extra chromosome 21 in relation to different factors: advanced maternal age, maternal serum human chorionic gonadotropin (hormone of placental origin), severity of the disease, gestational age at diagnosis and fetal gender. We found that the increased frequency of paternal origin of nondisjunction in trisomy 21-affected fetuses cannot obviously be explained by factors leading to selective loss of paternal origin fetuses.     

Parental origin of the extra chromosomes in polysomy X

Five polymorphic index markers were analyzed by polymerase chain reaction (PCR) to ascertain the parental origin of the extra X chromosomes in seven polysomic cases (one 49,XXXXX, three 49,XXXXY, two 48,XXXY, and one 48, XXYY). All four X chromosomes in 49, X polysomies were maternal in origin and the extra X chromosomes in 48 X polysomies were paternal. In each case the multiple X chromosomes were contributed by a single parent. Taken together with previously reported cases, these data support a single mechanism of sequential nondisjunction during either maternal or paternal gametogenesis as the cause of higher order sex chromosome polysomy.     

Maternally transmitted extra ring(21) chromosome in a boy with Down's syndrome

Summary An 11-month-old boy with typical Down's syndrome is presented. His karyotype was 47,XY,+r(21); the erythrocyte superoxide dismutase-1 (SOD-1) activity was elevated. His phenotypically normal mother showed 46,XX,r(21) karyotype and normal SOD-1 activity. Analysis of chromosomal heteromorphism revealed that in addition to the ring, a normal chromosome 21 was transmitted from the mother.     

The origin of an extra chromosome 21 in families of children with Down syndrome

These are the first studies on the origin of nondisjunction of trisomy 21 in the USSR. Parental contribution was established in 84 of 140 families observed. In 66% cases the nondisjunction took place in oogenesis and in 34% cases - in spermatogenesis. Among the children, who inherited the additional chromosome from father, boys predominate. Compilative work on all the data available concerning the origin of the 21 nondisjunction has been performed; the factors favouring nondisjunction in I and II mitotic divisions in female meiosis, both genetical and age-dependent, have been considered. The great importance of the disturbances taking place in spermatogenesis for etiology is emphasized. It is proved that somatic hyperploidy does not serve as an indicator of predisposition for chromosome nondisjunction in meiosis.     

Origin of extra chromosome in Patau syndrome

Summary Five live-born infants with Patau syndrome were studied for the nondisjunctional origin of the extra chromosome. Transmission modes of chromosomes 13 from parents to a child were determined using both QFQ- and RFA-heteromorphims as markers, and the origin was ascertained in all of the patients. The extra chromosome had originated in nondisjunction at the maternal first meiotic division in two patients, at the maternal second meiosis in other two, and at the paternal first meiosis in the remaining one.Summarizing the results of the present study, together with those of the previous studies on a liveborn and abortuses with trisomy 13, nondisjunction at the maternal and the paternal meiosis occurred in this trisomy in the ratio of 14:3. This ratio is not statistically different from that inferred from the previous studies for Down syndrome. These findings suggest that there may be a fundamental mechanism common to the occurrence of nondisjunction in the acrocentric trisomies.     

Retrospective study of the parental origin of the extra chromosome in trisomy 18 (Edwards syndrome)

The parental origin of the extra chromosome in trisomy 18 was traced in 30 informative families using highly polymorphic (CA) repeats mapped on the long arm of chromosome 18. Proband DNA was recovered from slides of chromosome preparations in 28 cases and from paraffin-embedded tissues in two cases. The extra chromosome was found to be of maternal origin in 26 cases (86.7%), and paternal origin in 4 cases (13.3%).     

Parental origin of chromosome abnormalities in spontaneous abortions

Summary Tissue cultures were initiated from 130 spontaneous abortion specimens and 81 were successfully karyotyped. Chromosome abnormalities were found in 50 cases: 12 with XO, 27 with trisomy, 6 with triploidy, 1 with tetraploidy and 4 others. The parental origin was determined in 11 cases of trisomy for an acrocentric chromosome. Two cases were uninformative while 9 non-disjunctions were determined and occurred during meiosis I: 7 were maternal and 2 paternal (both with trisomy 21). Three out of 7 cases with trisomy 16 were informative and resulted from a divisional error during the first meiotic division in the mother. All cases of triploidy were informative. They resulted from non-reduction during meiosis I in the mother (2) or dispermy (4).     

Maternal and paternal origin of extra chromosome in trisomy 21

Summary Fluorescence markers were studied in 40 patients with Down's syndrome and their parents. In 11 cases maternal and in 5 cases paternal non-disjunction could be shown. The disjunctional event occurred in the first meiotic division in 5 maternal and in 2 paternal cases. A second division failure was found in 4 maternal and 2 paternal cases. In 3 cases the failure could either be of first or second meiotic division origin.     

The parental origin of the extra X chromosome in 47,XXX females.

We used X-linked DNA polymorphisms to study the parental origin of X chromosome nondisjunction in 28 47,XXX live-born females. Errors in oogenesis accounted for 26 of the cases, with the majority of these being attributable to an error at meiosis I. We observed an association between advanced parental age and meiosis I nondisjunction--but not meiosis II nondisjunction--in the maternally derived cases. In studies of recombination we found little evidence for an association between pairing failure and X chromosome nondisjunction, but our results suggest that increased recombination near the centromere may play a role in the etiology of the 47,XXX condition.     

Down's syndrome: chromosome analysis of 362 cases in Hungary.

A survey is given of the karyotypes observed in 362 children clinically diagnosed as cases of Down's syndrome from whom material was sent to 8 collaborating cytogenic laboratories in Hungary during the period 1965-1974. The sample studied cytogenetically constitutes about 20% of all children born in Hungary in this decade with Down's syndrome. The ways in which patients were selected for cytogenetic examinations could not be specified. In the sample, standard trisomy 21 was found in 91.7%, translocations in 3.9% and mosaicism in 4.4%. The mean age of the mothers of the children investigated was 29.05 years, a relatively low figure which may be explained by the decrease of the mean maternal age over the last decades.     

The origin of the extra chromosome 21 in Down syndrome. Studies of fluorescent variants and satelite association in 26 informative families.

Studies of fluorescence and other chromosomal variants were informative in 26 out of 72 families. Maternal nondisjunction was found in 19 and paternal in 7 cases. Satellite association studies of these parents and 94 controls from the same age group showed a highly significant increase in the satellite association index (AI) for chromosome 21 in the parents where the nondisjunctional event had taken place. The AI was also higher for chromosome 14. In addition, the parents who produced the normal gametes had significantly higher AI's for some acrocentrics than the controls. Exogenous factors increasing satellite association cannot be ruled out. The number of 21-21 association was significantly increased in the parents with nondisjunction in meiosis 1. The results indicate that satellite association may play a role in the etiology of Down syndrome.     

Parental origin of a ring 13 chromosome in a female with multiple anomalies

Summary A ring chromosome No. 13 was found in a 21-year-old female with multiple anomalies suggestive of 13q-syndrome. Chromosomes of the girl and her parents, studied by quinacrine staining, revealed the ring to be of paternal origin. Detailed study of the quinacrine banding pattern of the ring indicated loss of the most distal band of the long arm (13q34) and possible partial loss of the next adjacent long arm band (13q33). The short arm (13q11) was present but the stalk (13p12) and satellite (13p13) regions appeared to be missing.This work was supported in part by NIH grants HD 07997; Maternal and Child Health Services 970; HD 08236; CA 16747; by grants from the Medical Research Foundation of Oregon and by a Basil O'Connor Starter Research Grant.