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Biomedical subjects

J M Lalouel

Publications and source records attributed to J M Lalouel.

16 recordsLinked to original sources
PubMed1992

Molecular basis of human hypertension: role of angiotensinogen.

Essential hypertension is a common human disease believed to result from the interplay of multiple genetic and environmental determinants. In genetic studies of two large panels of hypertensive sibships from widely separated geographical areas, we obtained evidence of genetic linkage between the angiotensinogen gene (AGT) and hypertension, demonstrated association of AGT molecular variants with the disease, and found significant differences in plasma concentrations of angiotensinogen among hypertensive subjects with different AGT genotypes. The corroboration and replication afforded by these results support the interpretation that molecular variants of AGT constitute inherited predispositions to essential hypertension in humans.

Adult↗
PubMed1992

Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension.

The angiotensin converting enzyme (ACE) is a key component of the renin angiotensin system that contributes to the regulation of blood pressure (BP). Recent demonstration of linkage between the ACE locus and elevated BP in a rat model of hypertension has further emphasized ACE as a candidate gene in human hypertension. We report the localization of the ACE gene on the genetic map of chromosome 17, and identify an extremely polymorphic marker at the human growth hormone (hGH) locus which shows no recombination with ACE. We have found no evidence to support linkage between the ACE locus and hypertension, which suggests that mutations at the ACE locus do not commonly contribute to the pathogenesis of hypertension in our test population.

Base Sequence↗
PubMed1992

Genetic linkage of the human gene for phenylethanolamine N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, to DNA markers on chromosome 17q21-q22.

We have determined the genetic location of the human gene encoding phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholamine pathway catalyzing the synthesis of epinephrine (adrenaline) from norepinephrine. This gene is linked to DNA markers on the long arm of chromosome 17, q21-q22, most closely to the DNA markers MFD15 (D17S250) (Zmax = 15.0, theta = 0.065) and fLB17.1 (Zmax = 14.6, theta = 0.045). Multipoint linkage analysis placed the PNMT locus in the interval fLB17.1-CMM86 (D17S74), at 4 centiMorgans (cM) distal to fLB17.1, and at 17 cM proximal to CMM86. Mapping of the PNMT gene will provide the basis for genetic linkage studies in families with disease which might pathogenetically involve this enzyme. The human chromosomal region 17q21-22 identified here to harbour the PNMT gene may be syntenic to the chromosomal region in the stroke-prone spontaneously hypertensive rat (SHR-SP) recently linked to blood-pressure regulation. As an increase of PNMT activity has been associated with the development of hypertension in SHR-SP, it will be of interest to perform comparative mapping of the PNMT gene.

Animals↗
PubMed1992

Familial dyslipidaemic hypertension and other multiple metabolic syndromes.

Data from several different studies are reviewed suggesting that a subset of hypertension is associated with metabolic abnormalities involving lipids, insulin, and often obesity, all aggregating strongly in families. Persons with 'familial dyslipidaemic hypertension (FDH)' have an especially high risk of early coronary disease. The clinical and biochemical features of FDH are compared with Reaven's Syndrome X, familial combined hyperlipidaemia, dense LDL subfractions, diabetes, impaired glucose tolerance, central and general obesity, pre-diabetes, pre-hypertension, and heterozygous lipoprotein lipase deficiency. Some contribution from major gene effects is suggested in specific subsets reported in several different genetic studies reviewed in this report. It seems likely that multiple metabolic abnormalities are genetically heterogeneous. The data also suggest significant contributions from environmental factors such as diet and physical activity.

Coronary Disease↗
PubMed1992

Evidence for gene-environmental interactions in Utah families with hypertension, dyslipidaemia and early coronary heart disease.

1. Among 45,258 Utah families surveyed, about 4% have a strong aggregation of early coronary disease. In detailed clinical evaluation, about 21% of such high risk coronary families were found to have familial dyslipidaemic hypertension (FDH) and about 3% were found to have heterozygous familial hypercholesterolaemia (hFH). 2. Common and potentially modifiable environmental factors seem to play an important role in these high risk families. Non-genetic obesity promotes the expression of FDH. A high fat diet promotes the expression of FH. Cigarette smoking promotes earlier death in all coronary prone families. 3. Practical approaches are suggested for helping coronary prone pedigrees by applying our understanding of genetic and environmental factors that promote earlier coronary disease onset.

Adult↗
PubMed1979

Neural tube malformations: complex segregation analysis and calculation of recurrence risks.

Familial data on neural tube malformations in Great Britain were submitted to segregation analysis under the mixed model. Maternal and fetal factors cannot be discriminated in the absence of substantial bodies of data on spina bifida survivors who reproduce or on half-sibs. Early abortion studies would allow differential mortality in utero to be taken into account. After fitting the mixed and generalised single locus models, it is concluded that the multifactorial model can provisionally be used for calculation of recurrence risks. Pathogenic hypotheses implicating twinning seem to rest on little evidence.

Anencephaly↗
PubMed1979

Complex segregation analysis of diabetes mellitus.

Complex segregation analysis was applied to a sample of 12,293 nuclear families each with at least 1 diabetic patient. The families were divided into two groups depending on the proband's treatment: insulin-dependent (IDG) and insulin-independent (IIG). Heterogeneity analysis has revealed a highly significant difference in the IIG group when families were divided into different mating types. The higher recurrence risk was found in the group with affected mothers. Also evidence for a major recessive gene was found in the IGG group, while it was not possible to distinguish between the hypothesis for absence of a major locus and absence of polygenic inheritance in the IDG group. Risks to develop the disease were calculated for a few typical situations.

Adolescent↗
PubMed1979

A maximum likelihood map of chromosome 1.

Thirteen loci are mapped on chromosome 1 from genetic evidence. The maximum likelihood map presented permits confirmation that Scianna (SC) and a fourteenth locus, phenylketonuria (PKU), are on chromosome 1, although the location of the latter on the PGM1-AMY segment is uncertain. Eight other controversial genetic assignments are rejected, providing a practical demonstration of the resolution which maximum likelihood theory brings to mapping.

Chromosome Mapping↗
PubMed1978

Common and uncommon immunoglobulin haplotypes among Lebanese communities.

Allotypes of IgG1, IgG2, IgG3, and IgA2 subclasses were investigated in seven Lebanese communities (three Moslem and four Christian). The Gm-Am haplotypes found were mainly those prevalent in Caucasians with a low frequency of haplotypes usually observed in Africans and Orientals. The difference between highlanders and lowlanders as expressed by G2m(23) was highly significant and suggested a possible adaptation to selective pressure related to the gamma2 genes, possibly due to endemic malaria in the past. Exceptional Gm-Am haplotypes were unambiguously determined by family studies. Some were characterized either by a deletion or a repression or, in contrast, by a partial or total duplication of gamma genes. Two others had uncommon combinations of allotypes: Gm17;23;5,10,11,13,14 A2m1, where G1m (17) was present without G1m (1); and Gm3;23;5,14 A2m1, where the CH3 allotypes G3m (10,11,13) were lacking.

Gene Frequency↗
PubMed1977

Linkage mapping from pair-wise recombination data.

The problem of obtaining a genetic map of a linkage group from pair-wise recombination data is considered. A non-parametric approach is proposed, that does not require the definition of a mapping function, computation of coefficients of coincidence, nor knowledge of map length or sex differences in recombination. An application to Bridges and Morgan's (1923) data on chromosome 3 of Drosophila melanogaster is presented.

Chromosome Mapping↗
PubMed1977

Recurrence risks in complex inheritance with special regard to pyloric stenosis.

A large body of data on segregating families is used to generate specific recurrence risks conditional on sex and birth order for the best-fitting model of polygenes plus maternal effect. The method is general for diseases of complex inheritance, and lies within the competence of any serious genetic clinic. The question of whether consultees demand as much specificity should be subordinate to the question of whether counsellors are justified in providing less.

Birth Order↗