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Biomedical subjects

P Goodfellow

Publications and source records attributed to P Goodfellow.

At least 19 recordsLinked to original sources
PubMed1992

Inverted repeat structure of the Sry locus in mice.

The testis-determining gene Sry is located on the short arm of the mouse Y chromosome in a region known to have undergone duplications and rearrangements in comparison with the equivalent portion of the human Y chromosome. Detailed analysis of the Sry genomic locus reveals a further difference in that the mouse Sry open reading frame lies within 2.8 kilobases of unique sequence at the center of a large inverted repeat. This repeat, which is found in both Mus musculus musculus and Mus musculus domesticus Y chromosomes, is not present at the human SRY locus. Recombination involving the repeat region may have led to an 11-kilobase deletion, precisely excising Sry in a line of XY female mice.

Animals↗
PubMed1992

Chromosomal localisation of a pseudoautosomal growth gene(s).

Although recent molecular studies in patients with sex chromosome aberrations are consistent with a growth gene(s) being present in the pseudoautosomal region (PAR), the precise location has not been determined. In this report, we describe a Japanese boy and his mother with an interstitial deletion in Xp22.3 and review the correlation between genotype and stature in six cases of partial monosomy of the PAR. The results indicate that the region from DXYS20 to DXYS15 is the critical region for the putative growth gene(s).

Abnormalities, Multiple↗
PubMed1992

Short stature in a girl with a terminal Xp deletion distal to DXYS15: localisation of a growth gene(s) in the pseudoautosomal region.

This report describes a Japanese girl with short stature and a rearranged X chromosome. Her height remained below the 3rd centile growth curve for Japanese girls, and her predicted adult height (148.5 cm) was below her target height (163 cm) and target range (155 to 171 cm). Cytogenetic studies showed that the rearranged X chromosome was formed by a breakage at q26 and a transfer of the Xq fragment onto the tip of Xp. The abnormal X was always late replicating. No mosaicism was detected. Molecular analysis showed an Xp terminal deletion distal to DXYS15. Biochemical and radiological studies for short stature disclosed no abnormality. On the basis of height analysis of previous reports and a genotype-phenotype correlation of this patient, we propose that a growth gene(s) is present in the distal part of the pseudoautosomal region.

Blotting, Southern↗
PubMed1991

Functional reintroduction of human telomeres into mammalian cells.

Telomeric sequences of eukaryotes consist of short tandem repeats organized in arrays of variable length in which the guanine-rich strand runs 5'----3' toward the chromosomal end. The terminal repeats in yeast are the only elements necessary for telomere function in this organism. To test whether mammalian terminal repeats can function after reintroduction into a mammalian cell, a repeat-containing terminal fragment from a human chromosome was electroporated into a hamster-human hybrid cell line. In 6 of 27 independent transformants analyzed, the introduced sequences were found at the ends of chromosomes, based on all available criteria. Terminal restriction-fragment heterogeneity and the survival of these chromosomes demonstrate that these telomeres are functional. Cytogenetic evidence from one of these cell lines suggests that chromosome breakage with healing at the integration site is the mechanism responsible for the terminal location.

Animals↗
PubMed1991

Male development of chromosomally female mice transgenic for Sry.

The initiation of male development in mammals requires one or more genes on the Y chromosome. A recently isolated gene, termed SRY in humans and Sry in mouse, has many of the genetic and biological properties expected of a Y-located testis-determining gene. It is now shown that Sry on a 14-kilobase genomic DNA fragment is sufficient to induce testis differentiation and subsequent male development when introduced into chromosomally female mouse embryos.

Animals↗
PubMed1991

Four chromosomal breakpoints and four new probes mark out a 10-cM region encompassing the fragile-X locus (FRAXA).

We report the validation and use of a cell hybrid panel which allowed us a rapid physical localization of new DNA probes in the vicinity of the fragile-X locus (FRAXA). Seven regions are defined by this panel, two of which lie between DXS369 and DXS296, until now the closest genetic markers that flank FRAXA. Of those two interesting regions, one is just distal to DXS369 and defined by probe 2-71 (DXS476), which is not polymorphic. The next one contains probes St677 (DXS463) and 2-34 (DXS477), which are within 130 kb and both detect TaqI RFLPs. The combined informativeness of these two probes is 30%. We cloned from an irradiation-reduced hybrid line another new polymorphic probe, Do33 (DXS465; 42% heterozygosity). This probe maps to the DXS296 region, proximal to a chromosomal breakpoint that corresponds to the Hunter syndrome locus (IDS). The physical order is thus Cen-DXS369-DXS476-(DXS463,DXS477)-(DXS296, DXS465)-IDS-DXS304-tel. We performed a linkage analysis for five of these markers in both the Centre d'Etude du Polymorphisme Humain families and in a large set of fragile-X families. This establishes that DXS296 is distal to FRAXA. The relative position of DXS463 and DXS477 with respect to FRAXA remains uncertain, but our results place them genetically halfway between DXS369 and DXS304. Thus the DXS463-DXS477 cluster defines presently either the closest proximal or the closest distal polymorphic marker with respect to FRAXA. The three new polymorphic probes described here have a combined heterozygosity of 60% and represent a major improvement for genetic analysis of fragile-X families, in particular for diagnostic applications.

Blotting, Southern↗
PubMed1990

A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes.

A gene mapping to the sex-determining region of the mouse Y chromosome is deleted in a line of XY female mice mutant for Tdy, and is expressed at a stage during male gonadal development consistent with its having a role in testis determination. This gene is a member of a new family of at least five mouse genes, related by an amino-acid motif showing homology to other known or putative DNA-binding domains.

Amino Acid Sequence↗
PubMed1990

Population structure of the human pseudoautosomal boundary.

The mammalian sex chromosomes are composed of two genetically distinct segments: the pseudoautosomal region, where recombination occurs between the X and Y chromosomes, and the sex chromosome-specific parts. Between these two segments the human sex chromosomes differ by the insertion of an Alu element on the Y chromosome. We have surveyed the sequence variation in the boundary region using the polymerase chain reaction. Fifty seven Y and sixty X chromosomes from ten different human populations were analysed. The X chromosomes were found to be polymorphic at five positions in a 300-base-pair region. By contrast, all Y chromosomes were identical except for one distal polymorphism shared with the X chromosome.

Base Sequence↗
PubMed1989

Human homologs of two testes-expressed loci on mouse chromosome 17 map to opposite arms of chromosome 6.

Our laboratory has recently cloned and characterized two testes-expressed loci--the Tcp-10 gene family cluster and the D17Si11 gene--that map to the proximal portion of mouse chromosome 17. Human homologs of both loci have been identified and cloned. Somatic cell hybrid lines have been used to map the human homolog of D17Si11 to the short arm of chromosome 6 (p11-p21.1) along with homologs of other genes from the (Pim-1)-(Pgk-2) region of the mouse chromosome. The human TCP 10 locus maps to the long arm of chromosome 6 (q21-qter) along with homologs of other genes from the mouse chromosome 17 region between the centromere and Pim-1. The mapping of large portions of the mouse t haplotype to unlinked regions on human chromosome 6 rules out the possibility that a t-haplotype-like chromosome could exist in humans.

Alleles↗
PubMed1987

The human homologue of the mouse t-complex gene, TCP1, is located on chromosome 6 but is not near the HLA region.

Southern blot analysis indicates that there are four sequences in the human genome related to the mouse t-complex gene Tcp-1. All four genes were cloned and partial sequencing showed that one of them was a functional gene, and the other three were pseudogenes. The human sequences were all approximately 90% related to each other and 82-89% related to the mouse Tcp-1a sequence. Human TCP1 cDNA clones from both fibrosarcoma and B cell lines confirmed that there was a single expressed gene. mRNA transcripts of different sizes were accounted for by two different polyadenylation signals. The human TCP1 gene shared some amino acid substitutions with the mouse t-complex allele (Tcp-1a) which were not found in Tcp-1b. The functional human TCP1 gene was mapped, using a panel of somatic cell hybrids, as well as in situ analysis, to the long arm of chromosome 6 at 6q23-qter and thus is not closely linked to the HLA complex on the short arm. For this reason and others it is unlikely that there is a human equivalent of the mouse t-complex.

Amino Acid Sequence↗
PubMed1985

The human Thy-1 gene: structure and chromosomal location.

The human Thy-1 gene has been isolated and sequenced and compared to the rat and mouse Thy-1 genes. All three genes are organized in the same way: one exon encoding the majority of the signal peptide, another encoding the transmembrane segment, and a third encoding the remainder of the protein. One major structural difference between the human and rodent Thy-1 glycoproteins is that the former contains two instead of three glycosylation sites. RNA blot analysis of a human T-cell line expressing the T3 complex showed an absence of Thy-1 mRNA, excluding the possibility that Thy-1 represents one of the component chains of T3. The structural gene for human Thy-1 was localized to the long arm of chromosome 11 by nucleic acid hybridization to genomic DNA isolated from somatic cell hybrids.

Amino Acid Sequence↗
PubMed1985

Expression of Xg and the 12E7 antigen in primates.

Tests on cells from various non-human primates showed that expression of the 12E7 antigen is the same on cultured fibroblasts, peripheral blood lymphocytes and red blood cells. No quantitative polymorphism of 12E7 expression was observed in any of the animals tested. Tests on red blood cells of these primates confirm that anti-Xga and the monoclonal antibody 12E7 define different determinants.

Animals↗