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Biomedical subjects

M Ramsay

Publications and source records attributed to M Ramsay.

At least 109 records · Page 6Linked to original sources
PubMed1994

Yeast artificial chromosome cloning.

Yeast artificial chromosome (YAC) cloning systems enable the cloning of DNA stretches of 50 to well over 2000 kb. This makes it possible to study large intact regions of DNA in detail, by restriction mapping the YAC to produce a physical map and by examining the YAC for coding sequences or genes. YACs are important for their ability to clone the complete sequences of large genes or gene complexes that exceed the size limit for cloning in conventional bacterial cloning vectors like plasmids (up to 10 kb), bacteriophage (15 kb), and cosmids (50 kb). A major advantage of cloning in yeast, a eukaryote, is that many sequences that are unstable, underrepresented, or absent when cloned into prokaryotic systems, remain stable and intact in YAC clones. It is possible to reintroduce YACs intact into mammalian cells where the introduced mammalian genes are expressed and used to study the functions of genes in the context of flanking sequences. The correct protein processing mechanisms are present in the mammalian cells to ensure that a viable protein product is produced.

Animals↗
PubMed1994

Analysis of 40 known cystic fibrosis mutations in South African patients.

A total of 140 South African (SA) Caucasoid cystic fibrosis (CF) families were analysed for the common CF mutation, delta F508. The 52 non-delta F508 CF chromosomes in a subset of 127 of these families were also tested for 39 other known CF mutations. The most frequent mutation, apart from delta F508 (which occurs at a frequency of 79%), was G542X (1.3%). Four other mutations, R553X, S549N, 621 + 1G-->T and N1303K, were each found in single families. The other 35 mutations remained unidentified in this sample of CF families. Since 83% of SA Caucasoid CF mutations have been identified, diagnosis by mutation analysis will be possible in only 69% of CF cases. When a diagnosis has been confirmed by a positive sweat test, a combination of linked marker analysis and mutation detection will be necessary if prenatal diagnosis and carrier detection are to be offered in the remaining families.

Cystic Fibrosis↗
PubMed1994

Absence of myotonic dystrophy in southern African Negroids is associated with a significantly lower number of CTG trinucleotide repeats.

Myotonic dystrophy (DM) is associated with an increased number of CTG repeats in the 3' untranslated region of the myotonin gene. Because DM has not been observed in southern African Negroids, a study of the CTG repeat polymorphism in this population was undertake. A total of 210 unrelated subjects was studied by PCR analysis of the trinucleotide repeat in the DM gene and the size and distribution of the CTG repeat were determined. The alleles ranged in length from five to 22 repeats. A previously undescribed BglI polymorphism was found which could lead to erroneous diagnosis of DM in people from this population. South African Negroids were found to have significantly fewer large repeat lengths than do white and Japanese populations. It is suggested that the occurrence of fewer large CTG repeats in the normal range may, in part, explain the absence of DM in southern African Negroids.

Africa, Southern↗
PubMed1994

The high frequency of the Hb B2 variant in the Herero population: a founder effect?

The beta-globin gene cluster haplotype associated with the delta-globin variant Hb B2 was determined in Herero individuals from six different families, in order to establish whether founder effect was responsible for the high frequency of this variant in the population. The electrophoretic detection of Hb B2 was confirmed at the molecular level by polymerase chain reaction, followed by Cfo I digestion. The haplotype associated with the Hb B2 chromosome was determined in two families, and was shown to be the same. In the remaining four families the haplotypes could not be established conclusively, but were consistent with the haplotype observed in the other two families. The high gene frequency of Hb B2 is thus likely to have resulted form founder effect.

Black People↗
PubMed1994

Pertussis immunisation in children with a family or personal history of convulsions: a review of children referred for specialist advice.

Recent guidelines recommend that children with a family or personal history of convulsions should receive all vaccinations. To determine vaccination status and adverse events following vaccination, questionnaires were sent to the general practitioners of 83 children referred for specialist advice between January 1988 and June 1991 in Redbridge Health Authority. Details of consultations within seven days of vaccination, and of any subsequent neurological or developmental problems were collected. Follow-up data were obtained for 77 of the 83 children (93%); 66 of whom had a family history, and 11 a personal history, of convulsions. Of the 66 children with a family history of convulsions, 57 received pertussis-containing vaccines, of whom one child was reviewed for a possible neurological event. Of the nine remaining children who received diphtheria-tetanus (DT) only vaccine, two children were reviewed for possible neurological events. Of the 11 children with a personal history of convulsions, nine received pertussis-containing vaccines and two received DT vaccines; none had any further neurological event. At late follow-up, none of the 77 children vaccinated had developed recurrent convulsions or any other neurological or developmental problems. Children with a family or personal history of convulsions who are given pertussis-containing vaccines seem unlikely to suffer adverse events or long-term neurological sequelae, and should be considered for all routine vaccinations in line with current recommendations.

Child↗
PubMed1994

The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids.

Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotypes are concordant within families, suggesting that there may be more than one mutation at the ty-pos OCA locus. Linkage studies carried out in 41 families have shown linkage between markers in the Prader-Willi/Angelman syndrome (PWS/AS) region on chromosome 15q11-q13 and ty-pos OCA. Analysis showed no obligatory crossovers between the alleles at the D15S12 locus and ty-pos OCA, suggesting that the D15S12 locus is very close to or part of the disease locus, which is postulated to be the human homologue, P, of the mouse pink-eyed dilution gene, p. Unlike caucasoid "ty-pos OCA" individuals, negroid ty-pos OCA individuals do not show any evidence of locus heterogeneity. Studies of allelic association between the polymorphic alleles detected at the D15S12 locus and ephelus status suggest that there was a single major mutation giving rise to ty-pos OCA without ephelides. There may, however, be two major mutations causing ty-pos OCA with ephelides, one associated with D15S12 allele 1 and the other associated with D15S12 allele 2. The two loci, GABRA5 and D15S24, flanking D15S12, are both hypervariable, and many different haplotypes were observed with the alleles at the three loci on both ty-pos OCA-associated chromosomes and "normal" chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa, Southern↗
PubMed1993

Exclusion of two candidate pigment loci, c and b, part of chromosome 11p, and 33 random polymorphic markers as the locus for tyrosinase-positive oculocutaneous albinism.

The locus for Tyrosinase-Positive Oculocutaneous Albinism (ty-pos OCA) has not yet been localised. The search for the ty-pos OCA locus has included a search for linkage to candidate pigment loci and a candidate chromosomal region, as well as a random search using highly polymorphic markers in 42 families, including 271 individuals of whom 79 are affected. The lod scores for the tyrosinase (TYR) locus (11q14-q21), homologous to the albino locus, c, in the mouse and the CAS2/TRP1 locus (9p22-pter), homologous to the brown locus, b, in the mouse were -5.89 and -7.22, respectively, at a recombination fraction of theta = 0.01, thus excluding them from being the ty-pos OCA locus. In the candidate chromosomal region, 11p, four loci (probes) were tested, SAA (pSAA82), CALC (pHC36), HBB (Gamma-globin haplotype) and an AC repeat polymorphism at the Wilm's Tumour locus (WT1). A portion of 11p was excluded with the following lod scores: pSAA82 lod = -2.05 at theta = 0.10; pHC36 lod = -3.87 at theta = 0.05; gamma-globin haplotype lod = -2.80 at theta = 0.10; and WT1 lod = -2.34 at theta = 0.10. Thirty-three polymorphic markers randomly distributed on 13 different chromosomes were all excluded from close linkage to ty-pos OCA.

Albinism, Oculocutaneous↗
PubMed1993

Haplotype analysis to determine the position of a mutation among closely linked DNA markers.

Positional cloning involves first finding linkage between an inherited phenotype (such as a disease) and a DNA marker, followed by the use of a variety of physical and genetic mapping techniques to move from linkage to mutation. If there is a founder effect within a population, crossovers are often rare between the mutation causing the phenotype and closely situated markers and increasing disequilibrium may be observed as the site of the mutation is approached. Standard coefficients of disequilibrium may, however, be insensitive to the relative position of close markers and the mutation, because they depend upon allele frequencies in the normal population compared to those of the founder chromosome. Using cystic fibrosis in European populations as a model system, alternative methods for determining the position of a mutation are discussed. These include haplotype parsimony and three-way interval likelihood analysis. Both methods predict the location of the major CF mutation accurately from a real set of more than 600 European CF chromosomes.

Alleles↗
PubMed1993

Non-organic failure to thrive: growth failure secondary to feeding-skills disorder.

In this article the authors propose that non-organic failure to thrive (FTT) is a growth failure secondary to feeding-skills disorder, and that this disorder is neurophysiological in origin. The symptoms of feeding-skills disorder were suggestive of an oral sensorimotor impairment which is usually present from birth or early life, but tends to go unrecognized. Data from 38 infants with non-organic and 22 infants with organic FTT demonstrated that early clinical symptoms of feeding impairment, and observed maternal and infant feeding behaviours and interactions, were similar for both groups, suggesting a need to redefine the term 'non-organic'.

Anthropometry↗
PubMed1992

Glucose-6-phosphate dehydrogenase (G6PD) electrophoretic variants and the PvuII polymorphism in southern African populations.

Southern African Bantu-speaking negroid and San populations were examined with regard to the glucose-6-phosphate dehydrogenase (G6PD) PvuII restriction fragment length polymorphism (RFLP) showing alleles of 4 kb and 1.6 kb, called Type 1 and Type 2, respectively. The standardized disequilibrium coefficient for the electrophoretic G6PD types and PvuII alleles in the Southern African population was 0.28. The molecular lesion causing the GdA mutation is the same in the San and Southern African negroid populations. GdA chromosomes are found in association with both the Type 1 and Type 2 alleles, whereas none of the 62 GdB chromosomes from the Southern African populations had the Type 2 allele. Five of the 44 GdB chromosomes studied in the American Black population had the Type 2 allele, indicating that the GdB allele in the two populations may have different origins. The presence of all 3 A- deficiency mutations in the G6PD A gene, in a region where the ancestral population was thought to have predominantly G6PD B, may be explained by their origin in Africa after the divergence of the races.

Africa, Southern↗
PubMed1992

Comparative study of pressor and heart rate responses to angiotensin II and noradrenaline in pregnant and non-pregnant women.

1. Twenty-eight healthy non-pregnant women and 28 women in the first or second trimester of pregnancy were studied. They were given an incremental intravenous infusion of either noradrenaline or angiotensin II. Pressor and heart rate responses were documented. 2. Dose-pressor response curves were constructed for the two agents in pregnant and non-pregnant women (n = 14 in each group). The regression parameters of slope and intercept were calculated, and were used to derive the variables of dose required to elicit a 10 mmHg rise in systolic or diastolic blood pressure. 3. The pressor response to angiotensin II was diminished in pregnancy, with approximately twice the dose being required to raise the systolic or diastolic arterial blood pressure as in non-pregnant subjects. 4. The systolic pressor response to noradrenaline was slightly diminished in pregnancy, but the diastolic pressor response was unchanged. There were no significant differences between the doses of noradrenaline required to elicit a 10 mmHg rise in systolic or diastolic arterial blood pressure in pregnant or non-pregnant subjects. 5. There was a diminution in the bradycardia evoked in response to both hormones in pregnancy. 6. We conclude that the well-documented pressor insensitivity to angiotensin II during pregnancy is a specific phenomenon, not a manifestation of a generalized reduction in vascular reactivity.

Angiotensin II↗
PubMed1992

Hereditary motor and sensory neuropathy type I, associated with aplasia cutis congenita: possible X-linked inheritance.

We report a family with possible X-linked recessive HMSN I with minor signs of the disease and abnormal sensory conduction studies evident in female carriers. There is a previously undescribed association with aplasia cutis congenita in both affected males, and a history of a severe skull defect in a third male child, who died at birth. The latter defect usually shows an autosomal dominant pattern of inheritance.

Adolescent↗
PubMed1992

The tyrosinase-positive oculocutaneous albinism locus maps to chromosome 15q11.2-q12.

Tyrosinase-positive oculocutaneous albinism (ty-pos OCA), an autosomal recessive disorder of the melanin biosynthetic pathway, is the most common type of albinism occurring worldwide. In southern African Bantu-speaking negroids it has an overall prevalence of about 1/3,900. Since the basic biochemical defect is unknown, a linkage study with candidate loci, candidate chromosomal regions, and random loci was undertaken. The ty-pos OCA locus was found to be linked to two arbitrary loci, D15S10 and D15S13, in the Prader-Willi/Angelman chromosomal region on chromosome 15q11.2-q12. The pink-eyed dilute locus, p, on mouse chromosome 7, maps close to a region of homology on human chromosome 15q, and we postulate that the ty-pos OCA and p loci are homologous.

Albinism, Oculocutaneous↗
PubMed1992

The Y-associated XY275 low allele is not restricted to indigenous African peoples.

The level of linkage disequilibrium between the XY275 MspI polymorphism and the X and Y boundaries was investigated in 21 different southern African populations. A full range of frequencies of the high allele was observed on the 1,013 X chromosomes studied, in keeping with published data. In previous studies fixation of the high allele on the Y chromosome was observed in all but two groups--a Pygmy and a Tsumkwe San population. However, in the present study of 673 Y chromosomes, the low allele was found to be associated with the Y chromosome in several different Bantu-speaking negroid groups, the Khoisan-speaking negroid Dama, the Khoisan, two groups of mixed ancestry, and the South African Asiatic-Indian population. The discovery of the low allele on Y chromosomes of caucasoid individuals suggests that more than one class of Y chromosome gave rise to the present-day non-African population. The data also fail to provide support for the theory that Africa is the site of origin of Homo sapiens, but they equally do not exclude it.

Africa, Southern↗