Biomedical subjects

J C Mulley

Publications and source records attributed to J C Mulley.

136 records · Page 8Linked to original sources

PubMed1979

Allozyme genotype--environment relationships in natural populations of Drosophila buzzatii.

Allozyme frequency data from natural populations of Drosophila buzzatii were analyzed for genotype--environment relationships. Allele frequency and heterozygosity at six loci polymorphic throughout eastern Australia and a number of environmental factors (both means and variabilities) were examined by a variety of multivariate techniques. Significant genotype--environment associations were found for five of the six loci, and after correcting for geographic location significant associations remained for Est-2 and Adh-1 gene frequencies and heterozygosities and for Pgm gene frequencies. The results are discussed in relation to selection and gene flow and provide the basis for laboratory studies to disentangle confounded effects of (1) environmental means and environmental variabilities and (2) allele frequency and heterozygosity, and thus to further test for and determine the nature of any natural selection at particular allozyme loci.

Alleles↗

PubMedDate not supplied

Fragile X syndrome and nephrogenic diabetes insipidus.

We describe a man with the fra(X) syndrome and nephrogenic diabetes insipidus. The disease loci for both conditions are in the region Xq27.3-q28. This is the first report of the fra(X) syndrome associated with another X-linked disorder. Analysis of DNA markers suggested that the association in this man was coincidental.

Diabetes Insipidus↗

PubMedDate not supplied

X-linked mental retardation with dystonic movements of the hands.

We describe a family with a syndrome of mental retardation, dystonic movements of the hands and dysarthria inherited in an X-linked recessive pattern. DNA marker studies gave a maximum lod score of 2.11 at theta of 0.00 for DXS41 with a likely localization of the gene to Xpter----Xp21.

Adolescent↗

PubMedDate not supplied

A non-syndromal form of X-linked mental retardation (XLMR) is linked to DXS14.

An analysis of the linkage of a non-syndromal form of X-linked mental retardation (MRX1) with a number of markers on the X chromosome was performed in a large pedigree. The affected males had moderate mental retardation; in all other clinical respects and cytogenetically they were normal. No recombinants were observed between the MRX1 gene and the marker DXS14 (p58.1) located at Xp11-cen (Z (max.) = 2.12 at theta = 0.00). Recombination was observed between the MRX1 gene and the markers DXS7 and DXYS1 which flank DXS14. This form of XLMR maps to the centromeric portion of the X-chromosome.

Chromosome Mapping↗

PubMedDate not supplied

Linkage studies with the gene for an X-linked syndrome of mental retardation, microcephaly and spastic diplegia (MRX2)

A family in which a gene (MRX2) is segregating for an X-linked syndrome of mental retardation, short stature, microcephaly, brachycephaly, spastic diplegia, small testes and possible intra-uterine growth retardation is described. There are 7 clearly affected males and one possibly affected infant in the family. The obligate carriers are normal. Linkage studies show a suggestion of linkage to loci near the centromere. The maximum lod score was 2.10 at theta = 0.11 for DXYS1, assuming the possibly affected male carried the MRX2 gene. There were lower lod scores suggestive of linkage with DXS7 (theta = 0.14; z = 1.29) and DXS94 (theta = 0.11; z = 1.22).

Adolescent↗

PubMedDate not supplied

A family with the Coffin Lowry syndrome revisited: localization of CLS to Xp21-pter.

We revisited a family with the Coffin-Lowry syndrome (CLS) first reported by Procopis and Turner in 1972. Twelve affected members are now known in 3 generations of which 9 were seen personally. DNA marker studies supported X-linkage with localization of CLS to Xp near DXS43 at p22.2-22.1 (theta = 0.001 Z = 2.71). Such linkage is reinforced by positive lod scores for DXS28 (theta = 0.00, Z = 0.90) and for DXS84 (theta = 0.09, Z = 1.56). Recombination with DXS84 and DXS164 places CLS distal to DMD in Xp21-pter.

Adult↗

PubMedDate not supplied

Characterization of new PCR based markers for mapping and diagnosis: AC dinucleotide repeat markers at the DXS237 (GMGX9) and DXS102 (cX38.1) loci.

Genomic insert DNAs from 45 probes representing 113.4 kb of the X chromosome were screened for AC dinucleotide repeat sequence. Two new AC repeat sequences were identified with length polymorphism based on variation in repeat copy number. One at DXS237 exhibits 44% heterozygosity and is potentially useful for rapid diagnosis and mapping of X-linked disorders in Xp22.3. The other, at DXS102 in Xq26, has 71% heterozygosity. This marker will improve accuracy of diagnoses by linkage for families with Börjeson-Forssman-Lehmann syndrome. Review of the literature has identified 31 PCR based markers on the X chromosome, with minimum heterozygosity of 50%, applicable to the mapping and diagnosis of X-linked disorders.

Base Sequence↗

PubMedDate not supplied

Nomenclature guidelines for X-linked mental retardation.

Nomenclature guidelines are proposed for non-specific and for syndromal forms of X-linked mental retardation. Non-specific mental retardations (MRX) are given unique symbols for each family (MRX1, MRX2, MRX3 ...). Syndromal mental retardations (MRXS) which do not as yet have specific symbols are given unique interim symbols for each syndrome (MRXS1, MRXS2, MRXS3 ...). The prerequisite for assignment of serial MRX and MRXS gene symbols is a minimum lod score (or multipoint lod score) of +2 between the MR locus and one or more X chromosome markers. Prior approval of availability for proposed gene symbols must be obtained from the Nomenclature Committee of the Human Gene Mapping Workshops.

Chromosome Mapping↗

PubMedDate not supplied

Use of linkage data obtained in single families: prenatal diagnosis of a new X-linked mental retardation syndrome.

Prenatal diagnosis was requested by an obligate carrier of a new syndrome of X-linked mental retardation. There was close linkage between the disease gene and the hypervariable VNTR marker DXS255 with a lod score of 4.82 at o = 0 (90% support interval 0.00-0.12). When the request for prenatal diagnosis was made, additional family members were examined, resulting in an amended lod score of 6.71 at o = 0.0 (90% support interval 0.00-0.09). There were no informative flanking markers at the time of the request for prenatal diagnosis; hence it proceeded by 2 point linkage analysis. The fetus was female with a carrier risk in the interval of 91-100%. Given the limitations of the mapping data available for this disorder at the time of the request, the options of accepting or rejecting this as a case for prenatal diagnosis were carefully considered. Whilst prenatal diagnosis based on fetal sexing would be sufficient to prevent the birth of an affected child, the magnitude of the known two-point lod score between DXS255 and the disease gene provided a means for diagnosis with an accuracy between 91 and 100%.

Female↗

PubMedDate not supplied

Characterisation and expression of a large, 13.7 kb FMR2 isoform.

FMR2 is the gene associated with FRAXE fragile site non-specific mental retardation (FRAXE MRX). Previously a male patient was identified with developmental delay and speech problems who had a deletion within intron 3 of FMR2. No known FMR2 exonic sequences were missing in this patient. Detailed northern blot analysis revealed existence of a new large isoform of FRM2 in foetal brain. This isoform was characterised and found to be due entirely to an addition of an extra 4.9 kb of the 3' UTR to the previously characterised 8.755 kb FMR2 transcript. This excluded involvement of the large FMR2 isoform in the MRX phenotype of three individuals now known to have the same deletion of intron 3 FMR2 sequences. Expression studies on the new 13.7 kb FMR2 isoform show that it is expressed predominantly in foetal brain and adult pituitary gland, whilst the expression of the shorter previously characterised 8.755 kb isoform is broader, including testis, thymus and placenta. Possible consequences of the alternative processing and expression of FMR2 for the molecular pathology of FRAXE MRX are discussed.

Gene Expression↗