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N A Affara

Publications and source records attributed to N A Affara.

At least 19 recordsLinked to original sources
PubMed1992

Evolution of DNA sequence homologies between the sex chromosomes in primate species.

Cloned DNA sequences from 18 X-Y homologous loci have been used to examine the evolution of regions of homology between the human X and Y chromosomes. The pattern of X-Y linkage in different primate species has enabled the charting of the chronology of their appearance and removal from the sex chromosomes during evolution. Examination of the pattern of differences in restriction enzyme sites at different loci has been used to estimate the degree of divergence in three different regions of homology. These studies have indicated that (1) blocks of homology have arisen at different points in evolution, (2) different regions of homology are heterogeneous in composition in that they contain X-Y homologous sequences of different age, and (3) the combination of X and Y locations together with the point of evolutionary origin has defined five new patterns of homology.

Animals↗
PubMed1992

A molecular deletion map of the Y chromosome long arm defining X and autosomal homologous regions and the localisation of the HYA locus to the proximal region of the Yq euchromatin.

41 Y-linked DNA probes that detect sequences on the Y chromosome long arm have been used to analyse genomic DNA from a series of 23 patients with deletions of Yq. Southern blot analysis has differentiated 15 distinct breakpoints, which divide Yq into 14 mapping intervals. From the pattern of DNA sequences present in each patient, it has been possible to produce a congruent deletion map, with the exception of two cases which are not compatible with the consensus order. These patients can be explained by the presence of inversion polymorphisms on Yq in the general population or by complex rearrangements induced during the formation of the deleted chromosomes. The distribution of sequences on the Y long arm has defined distinct regions of homology with autosomes, the Y short arm and the long and short arms of the X. A number of the patients have been typed for the presence or absence of H-Y antigen (as determined by the cytotoxic T-cell assay) and it has been possible, from analysis of informative cases, to assign the locus to the proximal region of the Yq euchromatin.

Cell Line↗
PubMed1992

Fine mapping of the McLeod locus (XK) to a 150-380-kb region in Xp21.

McLeod syndrome, characterized by acanthocytosis and the absence of a red-blood-cell Kell antigen (Kx), is a multisystem disorder involving a late-onset myopathy, splenomegaly, and neurological defects. The locus for this syndrome has been mapped, by deletion analysis, to a region between the loci for Duchenne muscular dystrophy (DMD) and chronic granulomatous disease (CGD). In this study, we describe a new marker, 3BH/R 0.3 (DXS 709), isolated by cloning the deletion breakpoint of a DMD patient. A long-range restriction map of Xp21, encompassing the gene loci for McLeod and CGD, was constructed, and multiple CpG islands were found clustered in a 700-kb region. Using the new marker, we have limited the McLeod syndrome critical region to 150-380-kb. Within this interval, two CpG-rich islands which may represent candidate sites for the McLeod gene were identified.

Blotting, Southern↗
PubMed1991

An X-linked zinc finger gene mapping to Xq21.1-q21.3 closely related to ZFX and ZFY: possible origins from a common ancestral gene.

We describe a new zinc finger gene sequence (CMPX1 or HGM symbol ZNF6; isolated by cross-hybridization of ZFY to clones in a testis cDNA library) which possesses a zinc finger domain closely related to the transcriptional activator gene ZFX. The putative acidic activation domain is only 11.5% homologous with ZFX, whereas the putative DNA binding domain shares 75% homology and shows the same organisation composed of a basic two fingered repeat unit. ZNF6 has an unusually large 5' untranslated region (UTR) of 1.2 Kb which contains 26 potential ATG initiation codons, only one of which is associated with a long open reading frame. Southern and Northern blot analysis has shown that this 5' UTR is shared with many other sequences in the genome and transcribed associated with a large range of mRNA species. In situ hybridisation, analysis of somatic cell hybrids and male individuals carrying deleted X chromosomes have mapped the gene to Xq21.1-q21.3. The gene is highly conserved amongst the primates, in the mouse and can be detected weakly in the genome of a metatherian mammal (possum). Dosage in male and female mice indicates that it is also X-linked in this species. Possible origins of ZFX, ZFY and CMPX1 from a common ancestral gene are discussed.

Amino Acid Sequence↗
PubMed1991

Comparison of ZFY and ZFX gene structure and analysis of alternative 3' untranslated regions of ZFY.

We have cloned and sequenced transcripts from the X- and Y-linked zinc-finger genes ZFX and ZFY respectively and discuss a possible mechanism of post-transcriptional control by which these genes can be widely expressed but translated in only specific tissues. We report the identification of a novel 3'UTR (untranslated region) present in ZFY which is highly conserved among primates and contains a series of motifs implicated as mRNA instability determinants. These sequences can be substantially removed by polyadenylation directed from consensus (AATAAA) and non-consensus (AATATAAA) sequences in adult testis. The DNA-binding domains of the ZFY and ZFX proteins are compared using present models for zinc-finger/DNA interactions. Additionally, the genomic organisation of the ZFY coding sequence is presented as compared to that of ZFX.

Amino Acid Sequence↗
PubMed1991

Mapping of the von Hippel-Lindau disease locus to a small region of chromosome 3p by genetic linkage analysis.

Genetic linkage studies were performed in 22 families with von Hippel-Lindau (VHL) disease by using polymorphic DNA markers from distal chromosome 3p. Linkage was detected between VHL disease and the markers D3S18 (Zmax = 6.6 at theta = 0.0, confidence interval (CI) 0.00-0.06), RAF1 (Zmax = 5.9 at theta = 0.06, CI 0.01-0.16), and THRB (Zmax 3.4 at theta = 0.11). Multipoint linkage analysis localized the VHL disease gene within a small region (approximately 8 cM) of 3p25-p26 between RAF1 and (D3S191, D3S225) and close to the D3S18 locus. There was no evidence of locus heterogeneity, and families with and without pheochromocytoma showed linkage to D3S18. The identification of DNA markers flanking the VHL disease gene allows reliable presymptomatic and prenatal diagnosis to be offered to informative families.

Adrenal Gland Neoplasms↗
PubMed1990

Physical mapping of deletion breakpoints in patients with X-linked ichthyosis: evidence for clustering of distal and proximal breakpoints.

Previous studies have shown that approximately 80% of patients with X-linked ichthyosis have a total deletion of the steroid sulphatase (STS) locus which lies in Xp22.3-Xpter. We show by Southern analysis that a common core of sequences are absent in 78.6% of our cases, suggesting that the deletion breakpoints may be highly clustered. To characterize the region in more detail a long-range physical map of over 3 megabases (Mb) surrounding the STS locus was constructed using pulse-field gel electrophoresis. The map enabled the order of sequences tel-SI19-GMGXY3-[STS,GMGXY19]-GMGX9-[dic56 ,SIII2]-cen and the localization of the deletion breakpoints to be established. In ten cases the pulse-field evidence supports the clustering of breakpoints and indicates a deletion size of 2 Mb in most patients. Five CpG islands have been positioned around the STS locus and may be associated with other loci in the region involved in mental retardation and Kallman's syndrome. The map will be instrumental in an attempt to isolate and characterize the deletion breakpoints and to access other genes located in the region.

Arylsulfatases↗
PubMed1990

The secret of sex.

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Chromosome Deletion↗
PubMed1990

Study of X chromosome abnormality in XX males using bivariate flow karyotype analysis and flow sorted dot blots.

We have used bivariate flow karyotype analysis to quantify aberrant X chromosome size in 11 XX males. With one exception, the patients could be grouped into those with an X homologue difference greater than normal (Group A, n = 3) and into those whose X homologue difference could not be distinguished from female controls (Group B, n = 7). The range of sizes of the aberrant X chromosome in Y-sequence positive patients agrees with the variable nature of the X-Y interchange in these individuals as determined by the use of Y-specific DNA probes and Southern blotting analysis. In one patient it was possible to sort separately the normal and the X-Y interchanged homologues for dot blot analysis. The presence of Y sequences and an increased dose of the zinc finger gene, ZFY, were detected in the X-Y interchanged homologue. In preliminary studies of 5 male and 6 female controls, it was noted that a consistent difference between the two X homologues in females was found which could not be totally explained by errors of the fitting procedure. We suggest that this difference could be due to X inactivation and that the two X homologues in females might be distinguishable.

Autoradiography↗