Methylmalonic aciduria (MMA) is an autosomal recessive inborn error of metabolism that results from functional defects in methylmalonyl CoA mutase (MCM), a nuclear-encoded, mitochondrial enzyme that uses the vitamin B12 derivative, adenosylcobalamin (AdoCbl) as a cofactor. To date, 23 mutations have been identified at the MUT locus on the short arm of chromosome 6, causing the mut forms of MMA (mut complementation group; mut MMA, McKusick #251000). We now report seven novel mutations. Three were found in mut0 patients: R228Q (c759G→A) was found as a heterozygous change; G312V (c1011G→T) and 346delL (c1112delCTT) were both found as homozygous changes. Four mutations were found in mut– patients: A191E (c648C→A) and V633G (c1974T→G) were found in the same patient; 684insL (c2128insCTC) and L685R (c2130T→G) were both found as homozygous changes. The recent modelling of the human methylmalonyl CoA mutase allowed for an interpretation of the identified mutations. Hum Mutat 11:270–274, 1998. © 1998 Wiley-Liss, Inc.

We report on 3 cases with a fetal presentation of autosomal dominant polycystic kidney disease (ADPKD), which illustrate the variable expression of ADPKD during fetal life. Fetus 1 was diagnosed at 20 weeks of gestation by ultrasonography; a molecular prenatal diagnosis was performed at 10 weeks on fetus 2, a sib of fetus 1; and ADPKD was an incidental finding in fetus 3 who was aborted at 16 weeks for anencephaly. All pregnancies were terminated and pathologic studies of the fetal kidneys were performed. From these cases and a review of the literature, we draw the following conclusions: (1) so far, all fetal ADPKD kidneys that have been histologically studied have shown cystic dilatations; 28/32 of these fetuses had ultrasonographic manifestations of the disease and/or had sibs with an early-onset form of it; (2) these cysts can be found in newly formed nephrons (fetus 2), predominantly in the more mature nephrons of the deep cortex (fetus 1) or more sparsely distributed in the cortex (fetus 3); these different patterns may reflect different rates of progression of the disease; (3) in contrast to the histologic findings in adult kidneys, glomeruli seem to be predominantly affected in fetal ADPKD; (4) severe fetal expression of ADPKD seems to cluster in some families; and (5) so far, all DNA analyses performed in families with subjects presenting during the fetal or neonatal period have been consistent with linkage to the PKD1 locus.

Mammalian primary sex is determined by the presence or absence of the Y chromosome. However, little is known about the molecular processes through which the Y chromosome exerts its action. We applied recombinant DNA techniques to isolate mouse Y chromosomal fragments and described previously a clone designated as AC11 (Y. Nishioka and E. Lamothe. 1986. Genetics, 113:417-432). To obtain information on DNA sequences that flank AC11, we screened a mouse genomic library for the presence of AC11-related sequences and isolated over 50 positive clones. In this report we describe clones ACC2 and ACC3, both of which contain highly repetitive elements. Using a male-specific portion of these clones, we compared DNA's isolated from mice (Mus musculus, M. hortulanus, M. spretus, M. cookii, M. pahari, and M. platythrix), rat, hamster, and guinea pig and obtained results that agree with the phylogenetic relationships deduced from morphological and biochemical studies. The male-specific accumulation of the related sequences was found only in M. musculus, M. hortulanus, and M. spretus.

Using a mouse Y chromosomal repetitive sequence that differentiates between the Mus musculus musculus type Y chromosome and the M. m. domesticus type Y chromosome, we studied the Y chromosome in M. m. molossinus, M. m. castaneus and M. m. subspecies specimens recently trapped in Japan, Taiwan and China as well as Asian mice maintained at the Jackson Laboratory and Litton Bionetics. Here we report that the M. m. musculus type Y chromosome predominates in Asian house mice and that Japanese mice maintained at some laboratories may not represent typical M. m. molossinus .

SummaryUsing a mouseYchromosomal repetitive sequence that differentiates between theMus musculus musculustypeYchromosome and theM. m. domesticustypeYchromosome, we studied theYchromosome inM. m. molossinus, M. m. castaneusandM. m.subspecies specimens recently trapped in Japan, Taiwan and China as well as Asian mice maintained at the Jackson Laboratory and Litton Bionetics. Here we report that theM. m. musculustypeYchromosome predominates in Asian house mice and that Japanese mice maintained at some laboratories may not represent typicalM. m. molossinus.

The human Y chromosome is highly heterochromatic and consists mainly of repetitive sequences, of which 3.4 kb HaeIII or EcoR1 fragments represent the most abundant species. From a flow-sorted human Y chromosomal library, we isolated 15 clones containing sequences highly homologous to this major repetitive sequence. Although the size of inserts varied from 0.7 to 3.8 kb, their hybridization patterns to human genomic DNA were indistinguishable from each other. These repetitive sequences unambiguously detected the presence of the Y chromosome in a male-female DNA mixture of which 5% was derived from male cells. Thus, these clones would be useful molecular tools to detect contaminating male cells in clinical materials.

Annals of the New York Academy of SciencesVolume 463, Issue 1 p. 323-326 Isolation of a Mouse DNA Fragment Preferentially Hybridizing to the Y Chromosomea YUTAKA NISHIOKA, YUTAKA NISHIOKA Department of Biology and Centre for Human Genetics McGill University Montreal, Quebec, Canada H3A IBISearch for more papers by this authorESTELLE LAMOTHE, ESTELLE LAMOTHE Department of Biology and Centre for Human Genetics McGill University Montreal, Quebec, Canada H3A IBISearch for more papers by this author YUTAKA NISHIOKA, YUTAKA NISHIOKA Department of Biology and Centre for Human Genetics McGill University Montreal, Quebec, Canada H3A IBISearch for more papers by this authorESTELLE LAMOTHE, ESTELLE LAMOTHE Department of Biology and Centre for Human Genetics McGill University Montreal, Quebec, Canada H3A IBISearch for more papers by this author First published: May 1986 https://doi.org/10.1111/j.1749-6632.1986.tb21585.x a This study was supported by a grant from the Medical Research Council of Canada. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 BISHOP, C. E., G. GUELLAEN, A. D. GELDWERTH, R. VOSS, M. FELLOUS & J. WEISSENBACH, 1983. Nature 303: 831–832. 10.1038/303831a0 CASPubMedWeb of Science®Google Scholar 2 LAMAR, E. E. & E. PALMER. 1984. Cell 37: 171–177. 10.1016/0092-8674(84)90312-X CASPubMedWeb of Science®Google Scholar 3 SINGH, L., I. F. PURDOM & K. W. JONES. 1980. Chromosoma (Berl.) 79: 137–157. 10.1007/BF01175181 CASPubMedWeb of Science®Google Scholar 4 SINGH, L., I. F. PURDOM & K. W. JONES. 1981. Cold Spring Harbor Symp. Quant. Biol. 45: 805–814. 10.1101/SQB.1981.045.01.099 CASPubMedWeb of Science®Google Scholar 5 SINGH, L. & K. W. JONES. 1982. Cell 28: 205–216. 10.1016/0092-8674(82)90338-5 CASPubMedWeb of Science®Google Scholar 6 CATTANACH, B. M., C. E. POLLARD & S. G. HAWKES. 1971. Cytogenetics 10: 318–337. 10.1159/000130151 PubMedWeb of Science®Google Scholar 7 BROWN, S. D. M. & G. A. DOVER. 1981. J. Mol. Biol. 150: 441–456. 10.1016/0022-2836(81)90374-0 CASPubMedWeb of Science®Google Scholar 8 HELLER, R. & N. ARNHEIM. 1980. Nucleic Acids Res. 8: 5031–5042. 10.1093/nar/8.21.5031 CASPubMedWeb of Science®Google Scholar 9 MEUNIER-ROTIVAL. M. & G. BERNARDI. 1984. Nucleic Acids Res. 12: 1593–1608. 10.1093/nar/12.3.1593 CASPubMedWeb of Science®Google Scholar Volume463, Issue1Second Colloquium in Biological Sciences: Intercellular Communication and Cell Surface ReceptorsMay 1986Pages 323-326 ReferencesRelatedInformation

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.