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Showing papers on "Chromosome 21 published in 1986"



Journal Article
TL;DR: The results suggest a deletion map of the Y chromosome, in which each of the 23 Y-specific restriction fragments tested can be assigned to one of seven intervals, and the polarity of this map with respect to the long and short arms of theY chromosome is established.
Abstract: The genomes of 27 individuals (19 XX males, two XX hermaphrodites, and six persons with microscopically detectable anomalies of the Y chromosome) were analyzed by hybridization for the presence or absence of 23 Y-specific DNA restriction fragments. Y-specific DNA was detected in 12 of the XX males and in all six individuals with microscopic anomalies. The results are consistent with each of these individuals carrying a single contiguous portion of the Y chromosome; that is, the results suggest a deletion map of the Y chromosome, in which each of the 23 Y-specific restriction fragments tested can be assigned to one of seven intervals. We have established the polarity of this map with respect to the long and short arms of the Y chromosome. On the short arm, there is a large cluster of sequences homologous to the X chromosome. The testis determinant(s) map to one of the intervals on the short arm.

331 citations


Journal ArticleDOI
TL;DR: Human and mouse cell clones that overproduce the hSOD‐1 had altered properties; they were more resistant to paraquat than the parental cells and showed an increase in lipid peroxidation, consistent with the possibility that gene dosage of hS OD‐1 contributes to some of the clinical symptoms associated with Down's syndrome.
Abstract: The 'housekeeping' enzyme Cu/Zn-superoxide dismutase (SOD-1) is encoded by a gene residing on human chromosome 21, at the region 21q22 known to be involved in Down's syndrome. The SOD-1 gene and the SOD-1 cDNA were introduced into mouse L-cells and human HeLa cells, respectively as part of recombinant plasmids containing the neoR selectable marker. Human and mouse transformants were obtained that expressed elevated levels (up to 6-fold) of authentic, enzymatically active human SOD-1. This enabled us to examine the consequences of hSOD-1 gene dosage, apart from gene dosage effects contributed by other genes residing on chromosome 21. Human and mouse cell clones that overproduce the hSOD-1 had altered properties; they were more resistant to paraquat than the parental cells and showed an increase in lipid peroxidation. The data are consistent with the possibility that gene dosage of hSOD-1 contributes to some of the clinical symptoms associated with Down's syndrome.

323 citations


Journal ArticleDOI
17 Jan 1986-Cell
TL;DR: To identify gene products that function stoichiometrically in mitotic chromosome transmission, genes were cloned on high copy number plasmids and transformed into yeast cells, and the transformants were examined for an increase in the frequency of mitotic chromosomes loss or recombination resulting from the gene imbalance.

315 citations


Journal ArticleDOI
TL;DR: It is suggested that the chromosome 17 and X alpha satellite subsets may be related components of a larger alphoid subfamily which have evolved from a common ancestral repeat into the contemporary chromosome-specific subsets.
Abstract: The centromeric regions of all human chromosomes are characterized by distinct subsets of a diverse tandemly repeated DNA family, alpha satellite. On human chromosome 17, the predominant form of alpha satellite is a 2.7-kilobase-pair higher-order repeat unit consisting of 16 alphoid monomers. We present the complete nucleotide sequence of the 16-monomer repeat, which is present in 500 to 1,000 copies per chromosome 17, as well as that of a less abundant 15-monomer repeat, also from chromosome 17. These repeat units were approximately 98% identical in sequence, differing by the exclusion of precisely 1 monomer from the 15-monomer repeat. Homologous unequal crossing-over is suggested as a probable mechanism by which the different repeat lengths on chromosome 17 were generated, and the putative site of such a recombination event is identified. The monomer organization of the chromosome 17 higher-order repeat unit is based, in part, on tandemly repeated pentamers. A similar pentameric suborganization has been previously demonstrated for alpha satellite of the human X chromosome. Despite the organizational similarities, substantial sequence divergence distinguishes these subsets. Hybridization experiments indicate that the chromosome 17 and X subsets are more similar to each other than to the subsets found on several other human chromosomes. We suggest that the chromosome 17 and X alpha satellite subsets may be related components of a larger alphoid subfamily which have evolved from a common ancestral repeat into the contemporary chromosome-specific subsets.

252 citations


Journal ArticleDOI
01 Jan 1986-Nature
TL;DR: Ch Chromosomal localization may provide a better understanding of the relationship of p53 to other human cellular genes and of its possible role in malignancies associated with specific chromosomal rearrangements.
Abstract: The p53 gene codes for a nuclear protein that has an important role in normal cellular replication. The concentration of p53 protein is frequently elevated in transformed cells. Transfection studies show that the p53 gene, in collaboration with the activated ras oncogene, can transform cells. Chromosomal localization may provide a better understanding of the relationship of p53 to other human cellular genes and of its possible role in malignancies associated with specific chromosomal rearrangements. A recent study mapped the human p53 gene to the long arm of chromosome 17 (17q21-q22) using in situ chromosomal hybridization. Here, by Southern filter hybridization of DNAs from human-rodent hybrids, we have localized the p53 gene to the short arm of human chromosome 17.

216 citations


Journal ArticleDOI
TL;DR: The structures in or surrounding the centromeres of S. pombe appear to be much more complex than those of the budding yeast Saccharomyces cerevisiae, which has three chromosomes.
Abstract: By cloning centromere-linked genes followed by partial overlapping hybridization, we constructed a 210-kb map encompassing the centromere in chromosome II and a 60-kb map near the centromere of chromosome I in the fission yeast Schizosaccharomyces pombe which has three chromosomes. Integration of the cloned sequences onto the chromosome and subsequent analyses of tetrads and dyads revealed an ~50 kb long domain located in the middle of the 210-kb map, tightly linked to the centromere and greatly reduced in meiotic recombination. This domain contained at least two classes of repetitive sequences. One, designated yn1, was specifically present in a particular chromosome and repeated three times in the 210-kb map of chromosome II. The other, designated dg, was located in all the centromere regions of three chromosomes. One (dgI) and two (dgIIa, dgIIb) copies of the dg were found in the maps of chromosomes I and II, respectively. The dgIIa and dgIIb were arranged with a 20-kb interval within the repetitive domain. In the centric region of chromosome III, 3−4 copies of the dg appeared to exist. By determining the nucleotide sequences of dgI and dgIIa, the dg was identified to be 3.8 kb long. The sequence homology was 99% between dgI and dgIIa. These extraordinarily homologous sequences seemed not to be transcribed into RNA nor to be encoding any protein. The larger part of the dg sequence was internally non-repetitious, a 600-bp region existed which consisted of stretches of several short repeating units. The structures in or surrounding the centromeres of S. pombe appear to be much more complex than those of the budding yeast Saccharomyces cerevisiae.

176 citations


Journal ArticleDOI
24 Jan 1986-Science
TL;DR: Two translocations of the human ets gene were found to translocate from chromosome 11 to 4 in the t(4;11)(q21;23), a translocation characteristic of a subtype of leukemia that represents the expansion of a myeloid/lymphoid precursor cell.
Abstract: Human probes identifying the cellular homologs of the v-ets gene, Hu-ets-1 and Hu-ets-2, and two panels of rodent-human cell hybrids were used to study specific translocations occurring in acute leukemias. The human ets-1 gene was found to translocate from chromosome 11 to 4 in the t(4;11)(q21;23), a translocation characteristic of a subtype of leukemia that represents the expansion of a myeloid/lymphoid precursor cell. Similarly, the human ets-2 gene was found to translocate from chromosome 21 to chromosome 8 in the t(8;21)(q22;q22), a nonrandom translocation commonly found in patients with acute myeloid leukemia with morphology M2 (AML-M2). Both translocations are associated with expression different from the expression in normal lymphoid cells of ets genes, raising the possibility that these genes play a role in the pathogenesis of these leukemias.

173 citations


Journal ArticleDOI
02 May 1986-Science
TL;DR: This work demonstrates how DNA sequence dosage analysis can be used to study genetic disorders that are not readily amenable to standard cytogenetic analysis.
Abstract: Most individuals with cat eye syndrome (CES) have a supernumerary bisatellited chromosome which, on the basis of cytogenetic evidence, has been reported to originate from either chromosome 13 or 22. To resolve this question, a single-copy DNA probe, D22S9, was isolated and localized to 22q11 by in situ hybridization to metaphase chromosomes. The number of copies of this sequence was determined in CES patients by means of Southern blots and densitometry analysis of autoradiographs. In patients with the supernumerary chromosome, four copies were found, whereas in one patient with a duplication of part of chromosome 22, there were three copies. Therefore, the syndrome results from the presence of either three or four copies of DNA sequences from 22q11; there is no evidence that sequences from other chromosomes are involved. This work demonstrates how DNA sequence dosage analysis can be used to study genetic disorders that are not readily amenable to standard cytogenetic analysis.

142 citations


Journal ArticleDOI
TL;DR: DNA analysis showed that the two deletions were different but included a common overlapping region likely to be essential for male determination, and showed a 46,X,Yp- karyotype.
Abstract: Structural anomalies of the sex chromosomes provide a means to study the location of genes responsible for sex determination. Recently, a type of sex reversal in humans, the 46,XX male, was shown to result in some cases from translocation of Y chromosome material to the X chromosome. In the present report, another type of sex reversal, the 46,XY female, is shown to result, in two cases, from small deletions of the short arm of the Y chromosome. Prometaphase chromosome analysis showed a 46,X,Yp- karyotype. Several Y chromosome-specific DNA probes were found to be deleted in the two female patients. DNA analysis showed that the two deletions were different but included a common overlapping region likely to be essential for male determination.

135 citations


Journal ArticleDOI
23 May 1986-Cell
TL;DR: The structural instability of a short dicentric artificial chromosome demonstrates that, although short artificial chromosomes segregate poorly in mitosis, they do attach to the mitotic spindle, and a model in which chromosome segregation is directed by the intercatenation of the segregating DNA molecules is discussed.

Journal ArticleDOI
TL;DR: CDNA clones containing sequences coding for the murine neural cell adhesion molecule (N-CAM) were used in Southern hybridizations on human genomic DNA and demonstrated approximately 90% homology between human and murine NCAM genes.
Abstract: cDNA clones containing sequences coding for the murine neural cell adhesion molecule (N-CAM) were used in Southern hybridizations on human genomic DNA and demonstrated approximately 90% homology between human and murine NCAM genes. In situ hybridization with one of these clones was performed on human metaphase chromosomes and allowed the localization of the human NCAM gene to band q23 of chromosome 11. The genes for two other cell surface molecules believed to be involved in cell-cell interactions, Thy-1 and the delta chain of the T3-T cell receptor complex, have recently been localized to the same region of chromosome 11 in man. Moreover, this region of the human chromosome 11 appears to be syntenic to a region of murine chromosome 9 that also contains the staggerer locus: staggerer mice show abnormal neurological features which may be related to abnormalities in the conversion of the embryonic to the adult forms of the N-CAM molecule.

Journal Article
TL;DR: An examination of the different combinations of two or more allelic series suggests that some alleles are not randomly distributed and raises the possibility of establishing a genealogy of the human Y chromosome.
Abstract: We have characterized a DNA probe (49f) that detects about 15 Y-specific TaqI bands corresponding to a low-copy number sequence. Five of these bands, each representing a single DNA fragment, can either be present, absent, or variable in length. Familial segregation studies have shown that the variations of these fragments are inherited in a Mendelian fashion and strictly Y-linked. A survey of 44 male individuals indicated that the five variable TaqI fragments detected by probe 49f can be considered as five independent allelic series. Each series represents the different and mutually exclusive allelic forms observed for a single DNA fragment. A total of 16 haplotypes, each defined by a different combination of the various forms of each of these five restriction fragment length polymorphisms, were observed among the 44 scored individuals. These TaqI restriction polymorphisms are not observed with other restriction digests and have therefore been attributed to point mutations. The five polymorphic fragments map to Yq11, a region that does not recombine with the X chromosome and are therefore not redistributed. This implies that an apparently independent reassortment of one of these series with respect to the others can be explained only on the basis of mutations that occurred several times (or reverted) during evolution of the Y chromosome. However, an examination of the different combinations of two or more allelic series suggests that some alleles are not randomly distributed and raises the possibility of establishing a genealogy of the human Y chromosome.

Journal ArticleDOI
17 Jan 1986-Cell
TL;DR: Two DNA sequences that reduce mitotic fidelity of chromosome transmission have been identified: MIF1 and MIF2.

Journal ArticleDOI
TL;DR: The occurrence of two distinct functional protooncogenes and their conservation of linkage positions in the three mammalian orders indicate that these two genes have been separate since before the evolutionary divergence of mammals.
Abstract: The mammalian protooncogene homologue of the avian v-ets sequence from the E26 retrovirus consists of two sequentially distinct domains located on different chromosomes. Using somatic cell hybrid panels, we have mapped the mammalian homologue of the 5' v-ets-domain to chromosome 11 (ETS1) in man, to chromosome 9 (Ets-1) in mouse, and to chromosome D1 (ETS1) in the domestic cat. The mammalian homologue of the 3' v-ets domain was similarly mapped to human chromosome 21 (ETS2), to mouse chromosome 16 (Ets-2), and to feline chromosome C2 (ETS2). Both protooncogenes fell in syntenic groups of homologous linked loci that were conserved among the three species. The occurrence of two distinct functional protooncogenes and their conservation of linkage positions in the three mammalian orders indicate that these two genes have been separate since before the evolutionary divergence of mammals.

Journal ArticleDOI
TL;DR: The Trisomy 16 (Ts16) mouse has been proposed as a model for Down Syndrome in humans, based on genetic homology between mouse chromosome 16 (MMU 16) and human chromosome 21 (HSA 21) as mentioned in this paper.

Book ChapterDOI
TL;DR: It is found that several genes exist on the B chromosome which help maintain its presence in populations through a system of non‐Mendelian inheritance and a number of methods have been developed for manipulating A chromosome dosage with B‐A translocations.
Abstract: The B chromosome in maize is small and highly heterochromatic. Its presence or absence in a plant has no apparent effect on the organism and the B is considered genetically inert. Studies with the maize B chromosome can be divided into two general categories: (1) analysis of the chromosome itself, including its origin, evolution, gene constitution, and DNA content, and (2) utilization of the chromosome in translocations to manipulate segments of standard (A) chromosomes. In the first category, an important finding has been that several genes exist on the B chromosome which help maintain its presence in populations through a system of non‐Mendelian inheritance. In the second type of research, a number of methods have been developed for manipulating A chromosome dosage with B‐A translocations. Segmental monosomics, trisomics, and tetrasomics have been constructed. Applications of the techniques are found mainly in cytological localization of genes and in construction of gene dosage series.

Journal ArticleDOI
TL;DR: The breakpoint regions of both translocation products of the (9;22) Philadelphia translocation of CML patient 83-H84 and their normal chromosome 9 and 22 counterparts have been cloned and analysed, strengthening the hypothesis that Alu-repetitive sequences can be hot spots for recombination.
Abstract: The breakpoint regions of both translocation products of the (9;22) Philadelphia translocation of CML patient 83-H84 and their normal chromosome 9 and 22 counterparts have been cloned and analysed. Southern blotting with bcr probes and DNA sequencing revealed that the breaks on chromosome 22 occurred 3' of bcr exon b3 and that the 88 nucleotides between the breakpoints in the chromosome 22 bcr region were deleted. Besides this small deletion of chromosome 22 sequences a large deletion of chromosome 9 sequences (greater than 70 kb) was observed. The chromosome 9 sequences remaining on the 9q+ chromosome (9q+ breakpoint) are located at least 100 kb upstream of the v-abl homologous c-abl exons whereas the translocated chromosome 9 sequences (22q-breakpoint) could be mapped 30 kb upstream of these c-abl sequences. The breakpoints were situated in Alu-repetitive sequences either on chromosome 22 or on chromosome 9, strengthening the hypothesis that Alu-repetitive sequences can be hot spots for recombination.

Journal Article
TL;DR: A panel of Chinese hamster X human somatic cell hybrids, each containing various portions of chromosome 21 as the only detectable human chromosome component, is used for regional mapping of cloned, chromosome 21-derived DNA sequences.
Abstract: We have used a panel of Chinese hamster X human somatic cell hybrids, each containing various portions of chromosome 21 as the only detectable human chromosome component, for regional mapping of cloned, chromosome 21-derived DNA sequences. Thirty unique and very low-repeat sequences were mapped to the short arm and three sections of the long arm. Three unique sequences map to the proximal part of the terminal band 21q22.3, and five to the distal part of this band. Some of these may represent parts of gene sequences that may be relevant to the pathogenesis of Down syndrome, as 21q22 is the area required to be present in triplicate for the full clinical picture.

Journal ArticleDOI
TL;DR: The c-ros gene joins the c-myb oncogene, which is distal to the c -ros gene on the long arm of human chromosome 6, as a candidate for involvement in chromosome 6q deletions and rearrangements seen in various malignancies.
Abstract: The human homolog, c-ros, of the transforming gene, v-ros, of the avian sarcoma virus, UR2, has been isolated from a human genomic library A single-copy fragment from the human c-ros genomic clone has been used to map the human c-ros homolog (ROS) to human chromosome region 6q16----6q22 by somatic cell hybrid analysis and chromosomal in situ hybridization Thus, the c-ros gene joins the c-myb oncogene, which is distal to the c-ros gene on the long arm of human chromosome 6, as a candidate for involvement in chromosome 6q deletions and rearrangements seen in various malignancies

Journal ArticleDOI
TL;DR: Cells from small (sigma) and large (lambda) trifluorothymidine-resistant (TFTr) colonies induced by chemical mutagen treatment of TK+/-L5178Y mouse lymphoma cells were examined for chromosomal abnormalities.
Abstract: Cells from small (sigma) and large (lambda) trifluorothymidine-resistant (TFTr) colonies induced by chemical mutagen treatment of TK+/-L5178Y mouse lymphoma cells were examined for chromosomal abnormalities. Analysis of G-banded metaphase chromosomes from 34 sigma-TFTr colonies revealed that cells from 20 (59%) possessed one or more chromosomal abnormalities. The most frequent (16/20 colonies) abnormality observed in cells from sigma-TFTr colonies involved the addition of extra chromatin to the distal region of one chromosome number 11. In 13 of these 16 colonies, the origin of the chromatin translocated to chromosome number 11 could not be identified; the chromatin was not missing elsewhere in the genome. The remaining three sigma-TFTr colonies with an abnormal chromosome number 11 had apparently whole chromosomes translocated, in tandem, to the distal region of chromosome number 11. Chromosomal abnormalities observed in cells from sigma-TFTr colonies with normal number 11 chromosomes included 2N/4N and 2N/4N/8N mosaicism (two colonies), a Robertsonian translocation involving chromosome 10 and a marker chromosome (one colony), and trisomy 7 (one colony). In most (14/16) sigma-TFTr colonies with structural damage to chromosome number 11, the cells within a colony were heterogeneous in that some possessed chromosomal damage whereas others were apparently normal. Analysis of chromosomes in cells from eight lambda-TFTr colonies revealed one colony in which all cells had a Robertsonian translocation involving chromosomes 1 and 16 plus other structural abnormalities. The chromosomes of cells from the remaining lambda-TFTr colonies were apparently normal.

Journal ArticleDOI
TL;DR: The γ-crystallins of the human eye lens are encoded by a multigene family of which at least six genes have recently been assigned to chromosome 2, and these genes are localized to the distal region of the long arm of chromosome 2 ( Region q33-36, most probably q34-35).
Abstract: The γ-crystallins of the human eye lens are encoded by a multigene family of which at least six genes have recently been assigned to chromosome 2 We have now localized these genes to the distal region of the long arm of chromosome 2 (region q33-36, most probably q34-35) using somatic cell hybrids containing different parts of this chromosome and by in situ hybridization The γ-crystallin genes map to the same chromosomal region as IDH-1 Similar linkage exists between the loci Len-1 and Idh-1 on mouse chromosome 1

Journal ArticleDOI
01 Jun 1986-Genetics
TL;DR: Based on the hybridization patterns against mouse Y chromosomal DNA, AC11 classified 16 inbred laboratory strains into two categories; those with the Mus musculus musculus type Y chromosome and those without, indicating that the amplification of AC11-related sequences in the mouse Y chromosome was a recent evolutionary event.
Abstract: The Y chromosome plays a dominant role in mammalian sex determination, and characterization of this chromosome is essential to understand the mechanism responsible for testicular differentiation. Male mouse genomic DNA fragments, cloned into pBR322, were screened for the presence of Bkm (a female snake satellite DNA)-related sequences, and we obtained a clone (AC11) having a DNA fragment from the mouse Y chromosome. In addition to a Bkm-related sequence, this fragment contained a Y chromosomal repetitive sequence. DNA isolated from the XX sex-reversed male genome produced a hybridization pattern indistinguishable to that obtained with normal female DNA, suggesting that the AC11 sequence is not contained within the Y chromosomal DNA present in the sex-reversed male genome. Based on the hybridization patterns against mouse Y chromosomal DNA, AC11 classified 16 inbred laboratory strains into two categories; those with the Mus musculus musculus type Y chromosome and those with the M.m. domesticus type Y chromosome. Three European subspecies of Mus musculus (M.m. brevirostris, M.m. poschiavinus and M.m. praetextus) possessed the M.m. domesticus type Y chromosome, whereas the Japanese mouse, M.m. molossinus, had the M.m. musculus type Y chromosome. The survey was also extended to six other species that belong to the genus Mus, of which M. spretus and M. hortulamus showed significant amounts of AC11-related sequences in their Y chromosomes. The male-specific accumulation of AC11-related sequences was not found in M. caroli, M. cookii, M. pahari or M. platythrix. This marked difference among Mus species indicates that the amplification of AC11-related sequences in the mouse Y chromosome was a recent evolutionary event.

Journal ArticleDOI
TL;DR: It is suggested that a clinically normal 28-year-old woman has a predisposition to irregular centromere separation and that chromosomes X, 18, and 21 are most susceptible to its action.
Abstract: A clinically normal 28-year-old woman had three conceptuses with trisomy 21 and one normal child. She showed minimal cytogenetic evidence of mosaicism: 4% of her blood cells and 6% of skin fibroblasts had trisomy 21. Also, 7% of her blood cells showed aneuploidy of the X chromosome which was associated with premature centromere division (PCD, X); 6% of fibroblasts showed trisomy 18, 10% of fibroblasts showed PCD,21, and 1% PCD, 18. It is unlikely that this woman is a constitutional mosaic for trisomies X, 18, and 21, all at low levels. We suggest that she has a predisposition to irregular centromere separation and that chromosomes X, 18, and 21 are most susceptible to its action.

Journal Article
TL;DR: A level of complexity is exposed in the D1S1 locus not revealed by earlier in situ hybridization studies, as the clone which defines this locus originates from human chromosome 3, but contains a 1.7-kilobase PstI-HindIII repetitive element that is also present on chromosome 1.
Abstract: We have investigated the segregation, in somatic cell hybrids, of the human D1S1 locus, previously assigned to 1p36 by in situ hybridization. We have shown that the clone which defines this locus, lambda Ch4A-H3, originates from human chromosome 3, but contains a 1.7-kilobase (kb) PstI-HindIII repetitive element that is also present on chromosome 1, probably distal to PGD. The clone recognizes restriction fragment length polymorphisms within the single-copy sequence on chromosome 3 and one for the enzyme StuI in the repeated sequence on chromosome 1. These experiments thus expose a level of complexity in the D1S1 locus not revealed by earlier in situ hybridization studies.

Journal ArticleDOI
TL;DR: The DNA probes met and pJ3.11 are derived from loci on chromosome seven that are closely linked to, and probably flanking, the gene mutation causing cystic fibrosis (CF), and may prove useful in confirming the order of loci around CF and in the prenatal diagnosis of this common autosomal recessive disease.
Abstract: The DNA probes met and pJ3.11 are derived from loci on chromosome seven that are closely linked to, and probably flanking, the gene mutation causing cystic fibrosis (CF). We have shown that mitotic chromosomes from the cell line MNNG-HOS, which contains an activated met oncogene, can induce morphological transformation of mouse NIH-3T3 cells. Southern analysis of isolated transfectant cell lines with cloned dispersed repetitive human DNA sequences as probes demonstrated that several lines of transformed NIH 3T3 cells had stabley incorporated large segments of chromosome seven DNA. Southern blot analysis also demonstrated the presence of met, pJ3.11 and several other single copy sequences that had been previously localised to chromosome 7 within the transgenomes. In this way a further four genetic markers were shown to be physically linked to met, and thus to CF. These probes may prove useful in confirming the order of loci around CF and in the prenatal diagnosis of this common autosomal recessive disease.

Journal Article
TL;DR: The cell hybrid and DNA library represent a rapid and efficient means to identify and isolate many polymorphic DNA markers close to and flanking the Huntington disease gene.
Abstract: Somatic cell hybrids were selected that retain a derivative chromosome 5 from an individual in which the p15.1-pter segment of chromosome 5 is replaced with the p15.1-pter segment of chromosome 4. Hybrids that retain this derivative chromosome exclusively were found to be positive for G8, a DNA marker closely linked to the Huntington disease gene on chromosome 4p. From one such hybrid, a segregant was isolated that had deleted the entire q arm of the derivative chromosome but retained the p arm intact as its only detectable human DNA. A complete recombinant DNA library was prepared from this cell line, and the inserts in approximately 1/3 of the recombinant phage with human DNA were shown to be derived from 4pter-4p15.1, which represents only approximately 1% of the total human genome. The cell hybrid and DNA library represent a rapid and efficient means to identify and isolate many polymorphic DNA markers close to and flanking the Huntington disease gene.

Journal Article
TL;DR: This genetic analysis raises the possibility that C5 and factor H are both encoded by complex loci composed of distinct structural and regulatory genes.
Abstract: Complementary DNA probes corresponding to the factor H and C5 polypeptides have been used to determine the chromosomal localizations of these two complement components. Both probes revealed complex and polymorphic arrays of DNA fragments in Southern blot analysis of mouse genomic DNA. Following the distribution of these bands in panels of somatic cell hybrids carrying various combinations of mouse chromosomes on a constant rat or Chinese hamster background allowed the localization of the C5-associated fragments to proximal chromosome 2 and the localization of the factor H-associated fragments to chromosome 1 or chromosome 3. Following the inheritance of DNA restriction fragment-length polymorphisms revealed by the probes in recombinant inbred mouse strains allowed the factor H-associated fragments to be mapped to Sas-1 on chromosome 1, and the C5-associated fragments to be mapped to Hc. Analysis of three-point crosses, in turn, placed the latter locus 19 cM distal to Sd on chromosome 2. We have designated the two loci Cfh and C5, respectively. This genetic analysis raises the possibility that C5 and factor H are both encoded by complex loci composed of distinct structural and regulatory genes.

Journal ArticleDOI
TL;DR: A genetic map of the short arm of chromosome 6 has been constructed on the basis of linkage studies with the eight markers and will be useful in the study of HLA-associated diseases.
Abstract: Four DNA sequences that reveal restriction fragment length polymorphisms (RFLPs) on the short arm of human chromosome 6 have been identified. Two of these sequences were isolated from recombinant DNA libraries enriched for DNA from human chromosome 6, one was isolated as a subclone from a human DNA segment having homology to an HLA class I sequence, and one was isolated by virtue of its homology to part of the insulin gene. Genetic linkage was determined among these four polymorphic sequences and several genes known to be on chromosome 6: glyoxylase I (GLO1), HLA-DR alpha, HLA-DQ alpha, and HLA-B. Additionally, two of the four RFLPs were regionally localized by using 53 deletion cell lines that had been typed for HLA-A, -B, and -DR, and for glyoxylase I. A genetic map of the short arm of chromosome 6 has been constructed on the basis of linkage studies with the eight markers. The map spans a minimum of 60 recombinational units and will be useful in the study of HLA-associated diseases.

Journal ArticleDOI
TL;DR: A stable ring chromosome 21 was found in an azoospermic man with an otherwise normal phenotype, and eight healthy females with r(21) were fertile, however, they were at risk for Down syndrome and spontaneous abortions.
Abstract: A stable ring chromosome 21 was found in an azoospermic man with an otherwise normal phenotype. Meiotic studies in another known azoospermic male with r(21) had indicated that breakdown of spermatogenesis resulted from pairing failure of chromosome 21, followed by degenerative changes in the chromosomes, before the cells had completed the first meiotic division. While primary sterility was a constant feature in the three adult males, eight healthy females with r(21) were fertile. However, they were at risk for Down syndrome and spontaneous abortions.