Biomedical subjects

J C Mulley

Publications and source records attributed to J C Mulley.

At least 127 records · Page 7Linked to original sources

PubMed1987

Molecular genetics of human chromosome 16.

The major diseases mapped to chromosome 16 are adult polycystic kidney disease and those resulting from mutations in the alpha globin complex. There are at least six other less important genetic diseases which map to this chromosome. The adenine phosphoribosyltransferase gene allows for selection of chromosome 16 in somatic cell hybrids and a hybrid panel is available which segments the chromosome into six regions to facilitate gene mapping. Genes which have been mapped to this chromosome or which have had their location redefined since HGM8 include APRT, TAT, MT, HBA, PKD1, CTRB, PGP, HAGH, HP, PKCB, and at least 19 cloned DNA sequences. There are RFLPs at 13 loci which have been regionally mapped and can be used for linkage studies.

Adenine Phosphoribosyltransferase↗

PubMed1986

New regional localisations for HAGH and PGP on human chromosome 16.

The chromosomal locations for the electrophoretic markers hydroxyacyl glutathione hydrolase (HAGH) and phosphoglycolate phosphatase (PGP) were examined using a human-mouse hybrid panel of chromosome 16. The assignment for HAGH was confirmed to chromosome 16 using a cell line with chromosome 16 as the only human chromosome. Both HAGH and PGP were present only in cell lines containing human 16p13. This localisation for PGP indirectly places the tightly linked genes for the alpha-globin cluster and adult polycystic kidney disease on 16p13.

Animals↗

PubMed1985

Genetic linkage analysis of epidermolysis bullosa dystrophica, Cockayne-Touraine type.

Genetic linkage relationships between 27 informative marker loci and the locus for epidermolysis bullosa dystrophica, Cockayne-Touraine type (EBD-CT), were examined in a single large kindred. Linkage could not be demonstrated to any of the marker loci, further adding to the exclusion map for EBD-CT. The dominant forms of EBD so far delineated by clinical criteria and electron microscopy remain genetically undefined in terms of loci and allelism. Further investigation will be undertaken using restriction fragment length polymorphisms mapped to regions outside the existing exclusion map.

Adolescent↗

PubMed1984

Genetic linkage analysis of epidermolysis bullosa simplex, Köbner type.

Genetic linkage relationships between a range of marker loci and the locus for epidermolysis bullosa simplex (EBS), Köbner type, were examined in a single kindred. A positive lod score of 1.2 at theta = 0.2 was found for Fy. To test the clinical observation that Köbner and Weber-Cockayne types may be the same disease determined by different alleles, published lod scores from definite Weber-Cockayne families were added to those from this study. A lod score of 1.8 was found at theta = 0.2. This value falls to 1.5 at theta = 0.2 when all families other than Ogna type are included. The Köbner variant studied is not closely linked to GPT and is therefore distinct from EBS1 (Ogna type). Linkage analysis is consistent with an hypothesis that Köbner and Weber-Cockayne types are determined by a single locus; however, further evidence is needed before this locus can be designated EBS2 and assigned to chromosome 1.

Chromosome Fragility↗

PubMed1983

A search for linkage in families with fragile sites.

Linkage relationships to unassigned and provisionally assigned genetic markers were examined from 53 families segregating for various fragile sites. Fragile sites were at Xq27, 2q13, 6p23, 9p21, 9p32, 10q23, 10q25, 11q13, 11q23, 12q13 and 16p12. No new assignments were made but extensive exclusion data are presented for the markers F13A, F13B, CHE2, K, TF, GPT, C3 and Lu arising from linkage comparisons with fragile sites and other genetic markers. Exclusions of at least 10 cM involving fragile site markers were made for F13A (6p23, 9q32, 10q25), F13B (10q23, 10q25, 16p12), CHE2 (16p12), K (10q23), TF (10q23, 10q25, 11q13), GPT (10q23, 10q25, 11q13), C3 (10q23, 10q25) and Lu (10q25, 11q13).

Chromosome Banding↗

PubMed1983

A new allele of alpha 1-antitrypsin: PI NADELAIDE.

The allele PI NADELAIDE (PI NADE) was named in accord with nomenclature guidelines and specifies a new co-dominant variant of alpha 1AT. Discovery was achieved by IEF and the isoelectric point of NADE is between N and NHAM. Familial inheritance of PI NADE was demonstrated and both PI M2NADE and PI M3NADE phenotypes were observed. The mobility of PI NADE is identical to PI M by both starch and agarose electrophoresis. PI NADE apparently confers normal alpha 1AT serum concentrations and is probably unrelated to disease.

Alleles↗

PubMed1983

Protease inhibitor (PI) phenotype of individuals with chromosomal fragile sites.

One hundred and four fragile sites were ascertained from 95 unrelated families. In each family the ancestry of the fragile site was traced as far as possible and the PI phenotype of the carrier in the earliest generation determined. Mildly deficient PI phenotypes were more prevalent than expected among earliest carriers of folate sensitive fragile sites, but not for BrdU dependent fragile sites. The significance of this finding is unclear and is based upon relatively small numbers. Another series of fragile site carriers would need to be studied and similar results found before the question of any relationship between PI phenotype and mutagenesis to fragile sites could be raised.

Chromosome Fragile Sites↗

PubMed1983

Regional localization for HLA by recombination with a fragile site at 6p23.

A family with a fragile site on chromosome 6 at band p23 was examined for recombination between the fragile site and HLA. Recombination was observed in four of the 20 offspring in whom it could occur. The estimate of the genetic length of chromosome between the fragile site and HLA is 20 centimorgans (cM) with a lower 95% probability limit of 8.5 cM, placing HLA proximal to the midpoint of 6p22. The most likely regional localization is at 6p21.3, which agrees closely with methods that do not involve recombination with the fragile site. This fragile site does not measurably disrupt recombination frequency, and the allele predisposing to expression of the fragile site is situated at the fragile site.

Chromosome Fragile Sites↗

PubMed1982

Genetic length of a human chromosomal segment measured by recombination between two fragile sites.

Two families were studied in which the same homolog of chromosome pair 10 expressed both the fragile sites on the long (q) arm at 10q23 and 10q25. Recombination between the fragile sites was observed in 3 of the 27 offspring in whom it could occur. The genetic length of chromosome between the fragile sites was 11 female centimorgans within a 95 percent probability interval of 4 to 28 centimorgans. This estimate of genetic length is comparable to those obtained with other methods.

Chromosome Banding↗

PubMed1982

Distribution of alpha 1-antitrypsin (PI) subtypes from newborns.

PI phenotypes were determined from 420 cord bloods from Adelaide. Allele frequencies for the subvariants PI*MI, PI*M2 and PI*M3 were 0.73, 0.14 and 0.09, respectively. The combined frequency of other alleles was 0.04. This relatively high level of variation makes PI useful for gene mapping, paternity testing and zygosity testing. For this locus the average probability of detecting non-paternity in this population is 28%.

Alleles↗

PubMed1982

Distribution of the GC (group-specific component) subtypes in cord bloods and blood donors.

The common allele, GC/1, was subtyped into GC*IF and GC*IS by isoelectric focusing, increasing the proportion of heterozygotes from 0.42 to 0.58. In a series of 200 blood donors and 200 cord bloods the allele frequencies were found to be: GC*IS = 0.59, GC*IF = 0.11, GC*2 = 0.30; and GC*IS = 0.54, GC*IF = 0.16, GC*2 = 0.30, respectively. These values were similar to frequencies obtained in studies of other Caucasian populations. The average probability of detecting non-paternity for this population is increased from 17% to 30% after subtyping GC 1.

Alleles↗

PubMed1982

Distribution of six TF C (transferrin) subtypes in cord bloods and blood donors.

Isoelectric focusing was used to subtype the common TF C phenotype into C1, C2 and C3, increasing the proportion of heterozygotes from virtually zero to 0.31. Five of the six subtypes of TF C were found in a series of 200 blood donors and 200 cord bloods. The frequencies of the three alleles were: TF*C1 = 0.80, TF*C2 = 0.17 and TF*C3 = 0.03 from cord bloods; and TF*C1 = 0.84, TF*C2 = 0.13 and TF*C3 = 0.03 from blood donors. These frequencies were comparable with estimates from other Caucasian populations. The average probability of detecting non-paternity for this population is increased to 11% by subtyping C into C1 and C2, and further increased to 15% by subtyping C into C1, C2 and C3.

Alleles↗

PubMed1982

Polymorphism of human galactose-1-phosphate uridyl transferase.

Frequencies for the electrophoretically detectable alleles of galactose-1-phosphate uridyl transferase were determined from 406 neonates in Adelaide. GALT*D and GALT*LA frequencies were 0.054 and 0.027, respectively. The expected proportion of heterozygotes was 15.3%, with a GALT N-D component of 10%. The distinction between GALT*D and GALT*LA is essential for estimation of the expected frequency of GALT DG genotypes, an unknown proportion of which are detected as 'deficient' from neonates on galactosaemia screen.

Alleles↗

PubMed1982

Further exclusions by deletion mapping.

Exclusions for unassigned markers were determined by deletion mapping at the following segments: (4)(p15.1 leads to 16.1) - F13A" F13B, TF; (4)(q27 leads to 31) - TF; (9)(p22 leads to pter) - F13B; (12)(p12) - TF; (12)(pter) - TF; (18)(q22) - F13A, K and LU; (19)(p or qter) - TF; (22)(pter leads to q11) - F13B. GC was excluded from (4)(p15.1 leads to 16.1) and (4)(q27 leads to 31). GALT was excluded from (9)(p22 leads to pter).

Chromosome Deletion↗

PubMed1981

Distribution of alpha 1-antitrypsin (PI) phenotypes in chromosome abnormalities.

PI phenotypes (including subtypes) were determined for 168 individuals with chromosomal abnormalities ascertained in Adelaide. These included patients with mosaicism, trisomy 21, trisomy 13, trisomy 18, and various sex chromosome aberrations (45,X, 47,XXX, 47,XXY, 47, XYY, and 48,XXXY). Data did not support an existing proposition that mildly deficient PI phenotypes predispose to abnormal chromosome segregation during mitosis of meiosis. Phenotypic distributions of each group were statistically similar to control populations of cord bloods and bloods donors.

Alleles↗

PubMed1981

A large kindred with an INV(3)(p25q23): clinical, cytogenetic and genetic marker studies.

A large kindred in which an inv(3)(p25q23) is segregating is described. At least two malformed children with the recombinant chromosome rec(3)dup(q23 leads to qter)del(p25 leads to pter) have been produced, both of whom have the characteristic trisomy 3q syndrome. Genetic marker studies showed that Pl and GM are not linked to the inversion break points. The Pl-GM linkage group has been excluded from much of chromosome 3 by deletion mapping and linkage analysis of this kindred.

Chromosome Aberrations↗

PubMed1980

Distribution of the six alpha 1-antitrypsin (PI) subtypes from a sample of blood donors.

The PI M phenotype of alpha 1-antitrypsin was classified into six subtypes determined by three alleles: PI*MI, PI*M2 and PI*M3. Phenotypes were classified by isoelectric focusing and their distribution agreed closely with Hardy-Weinberg expectations. The proportion of heterozygotes was 53%, which more than trebles the heterozygosity without subtyping, and is comparable to a recent estimate from U.S. whites.

Australia↗

PubMed1980

Additions to the exclusion map of man.

Exclusion mapping was applied to individuals with monosomic segments defined by chromosomal banding. A range of genetic markers and blood groups was determined resulting in new exclusions for unassigned markers at the following segments : (3)(p25 leads to pter) - JK, GPT, PI ; (4)(127 leads to 31) - MNS, JK, PI, C3, F13A, F13B ; (7))q22) - LU, F13A ; (12)(p12) - MNS ; (12)(p13) and (15)(q15) - GPT, C3 ; (12) (pter) and (19)(p or qter) - MNS, GPT, PI ; and (18)(q21 leads to 23) - MNS, JK, F13A. These exclusions may be useful for narrowing the regional localisations of any genetic markers subsequently assigned to the chromosome involved in the exclusion. No new gene assignments were made from cases where family data was available.

Chromosome Deletion↗