Nicole Créau-Goldberg

Maternal origin of a de novo balanced t(21q21q) identified by ets-2 polymorphism

SummaryMolecular investigations were done in a woman with a de novo balanced t(21q21q) discovered because of the birth of a trisomic 21 baby. Polymorphisms detected with probe ets-2 after MspI digestion showed that both chromosomes 21 involved in the rearrangement were of maternal origin. The most likely hypothesis is that of a disomic 21 oocyte fertilized by a nullisomic 21 sperm.

Submicroscopic duplication of chromosome 21 and trisomy 21 phenotype (Down syndrome).

SummaryA patient with the phenotype of trisomy 21 (Down syndrome) was found to have a normal karyotype in blood lymphocytes and fibroblasts. Assessment of the chromosome 21 markers SOD1, CBS, ETS2, D21S11, and BCEI showed partial trisomy by duplication of a chromosome segment carrying the SOD1, CBS, and ETS2 loci and flanked by the BCEI and D21S11 loci, which are not duplicated. This submicroscopic duplication at the interface of 21q21 and 21q22.1 reduces to about 2000–3000kb the critical segment the trisomy of which is responsible for the phenotype of trisomy 21.

Comparative gene mapping of man and Cebus capucinus: a study of 23 enzymatic markers

A total 23 enzymatic markers were analyzed in cell hybrids obtained between Cebus capucinus (CCA) fibroblasts and a Chinese hamster cell line. The following markers, or syntenic groups, could be localized in CCA chromosomes homologous to human chromosomes or chromosome segments: PGD-ENO1-PGM1, MDH1, IDH1, PGM2, PGM3-ME1, AK3, TPI-LDHB-PEPB, GPI, and SOD1. The following syntenic groups were observed but could not be localized: GUK1-FH and MPI-PKM2. The following loci could not be localized with full confidence: LDHA, NP, PEPD, ITP, and PGK.

Cytogenetic and molecular analysis of a de novo tandem duplication of chromosome 21

SummaryWe have characterised by cytogenetic and molecular analysis a de novo tandem duplication of chromosome 21. High resolution chromosome examination of lymphocytes revealed the following karyotype in 90% of the cells: 46,XY,dir dup (21)(pter→q22.300::q11.205 →qter). Of these cells, 10% showed a normal karyotype. Gene dosage of chromosome 21 sequences by a slot blot method indicated that the duplication extends from D21S16 to D21S55. In situ hybridization with probes close to the borders of the duplicated segment confirmed the gene dosage data and gave results consistent with a true tandem duplication of chromosome 21. Pulsed field gel electrophoresis of the patients DNA showed an abnormal restriction band common to D21S55 and D21S16, confirming that the junction point between the two homologous parts of the tandem chromosome brings these two sequences into proximity. Restriction fragment length polymorphism analysis indicated that the abnormal chromosome was maternal in origin and that the rearrangement of chromosome 21 could not have occurred at a post-zygotic stage of development but resulted from a recombination event during maternal gametogenesis. The possible mechanisms of formation of the abnormal chromosome are discussed, as is the presence of cells with normal chromosomes 21, in the patient.

The organization of two related subfamilies of a human tandemly repeated DNA is chromosome specific

SummarySeveral clones containing clusters of repetitive elements were isolated from a human chromosome 22 specific library. An EcoRI-XhoI fragment of 860bp was subcloned and was shown to belong to a family of tandemly repeated DNA linked to the Y-specific 3.4 kb HaeIII band. This probe hybridizes to several sets of sequences or subfamilies. The most abundant subfamily is a 1.8kb long sequence containing one EcoRV site, and in most repeats, one AvaII and one KpnI site. Using human-rodent somatic cell hybrid DNA, we have shown that this cluster is present on human chromosome 9 although presence on chromosome 15 is not excluded. Another subfamily, 6.1 kb long, appears to be exclusive of chromosome 16. By in situ hybridization with metaphasic chromosomes, these sets of repeats were mapped to the constitutive heterochromatin of a few chromosomes. Coexistence in one genome of long tandem repeats of distinct organization but similar length may represent the outcome of a continuous process of fixation of variant sequences. Homologous repeats are also abundant in four higher primate genomes (Orangutan, gorilla, chimpanzee, and man) but absent in other primates (African green monkey, rhesus monkey, baboon, and mouse lemur).

Gene mapping of the gibbon. Its position in primate evolution

SummaryComparative karyotyping of the Hylobatidae has revealed only very few chromosome homoeologies with other primates. Their position in the phylogenetic tree thus remains uncertain. With the hope that comparative gene mapping might allow overcoming these difficulties, somatic cell hybrids were obtained by fusion of fibroblasts from a Hylobates (Nomascus) concolor and cells from a HPRT-Chinese hamster cell line. Of 34 investigated enzyme markers, 20 could be mapped, and 7 syntenies were established. When compared with man, there were 7 synteny disruptions. These results strongly suggest that the Hylobatidae diverged from the common stem leading to the Pongidae after the Cercopithecoidae had diverged.

Physical map around the retinoblastoma gene: Possible genomic imprinting suggested by NruI digestion

A long-range restriction map constructed around the retinoblastoma (RB) gene by means of PFGE analysis allowed further definition of chromosomal rearrangements with a breakpoint within the gene, as well as of submicroscopic deletions. A serendipitous observation was that the NruI restriction pattern differs according to the parental origin of the rearrangement.

Partial physical map of human chromosome 21 from fibroblast and lymphocyte DNA

A partial physical map of the human chromosome 21 including 26 genes and anonymous sequences was established by pulsed-field gel electrophoresis analysis of restriction fragments obtained from lymphocyte and fibroblast DNAs. The sizes of the restriction fragments obtained by total digestion with eight different enzymes were compared in these two tissues. Differences resulting from the variations in the methylation state of the restriction sites were frequently observed. These differences and partial digestions were used to estimate the order and the distances between genes and sequences. Six linkage groups were defined: D21S13-D21S16, D21S1-D21S11, D21S65-D21S17, (D21S55,ERG)-ETS2, BCEI-D21S19-D21S42-D21S113-CBS-CRYA1, and COL6A2-S100B. For six intergenic distances the resolution of previous maps was significantly increased.

De novo t(2;13)(p24.3;q14.2) and retinoblastoma

SummaryThe two probes H3-8 and H2-42, known to be located in 13q14, were mapped by in situ hybridization to either side of the 13 breakpoint of an apparently balanced de novo t(2;13)(p24.3;q14.2) detected in a patient with retinoblastoma as the only phenotypic manifestation.

Gene mapping of Microcebus murinus (Lemuridae): a comparison with man and Cebus capucinus (Cebidae)

The karyotype of microcebus murinus (MIM) (lemuridae) is considered by Dutrillaux (1979) as the closest to the karyotype ancestral to all primates. A large number of homoeologies exists between the banding patterns of MIM chromosomes and those of man (HSA). We report a comparison of the gene maps of these two species which confirms most of these homoeologies. Fifteen cell hybrids were obtained by fusing MIM fibroblasts and an HPRT- Chinese hamster cell line. Twenty-seven enzyme markers were investigated. The following assignments were demonstrated: NP to chromosome MIM 2, homoeologous to HSA 14; the syntenic group PGD-ENO1-PGM1 to MIM 3, homoeologous to HSA 1p; LDHA to MIM 5, homoeologous to HSA 11; Me1 to MIM 6, homoeologous to HSA 6; the syntenic group LDHB-CS-PEPB-ENO2-TPI to MIM 7, homoeologous to HSA 12; the syntenic group AK1-AK3 to MIM 10, which we considered to be homoeologous to HSA 9 (we do not consider MIM 9 to be homoeologous to HSA 9, as does Dutrillaux, 1979); GOT1 to MIM 15, homoeologous to HSA 10; the syntenic group HPRT-G6PD-PGK-GLA to MIM X. Synteny dissociation in three hybrids suggests closer linkage between G6PD and HPRT than between PGK-GLA and HPRT. Three syntenic groups, known in man, were confirmed in MIM but could not be assigned with full confidence: ACP1-MDH1, MP1-PKM2, and PEPD-GPI. GUK1 and PEPC, known to be syntenic in man, were found to be asyntenic in MIM and could not be assigned. PGM2 and SOD1 could not be assigned. A comparison of these gene assignments with those known in Cebus capucinus showed a remarkable homoeology for six chromosomes of the two species.