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Biomedical subjects

R A Price

Publications and source records attributed to R A Price.

At least 55 records · Page 3Linked to original sources
PubMed1997

Apolipoprotein E genotype in schizophrenia: frequency, age of onset, and neuropathologic features.

Apolipoprotein E (ApoE) genotype has been found to affect the expression of a variety of neuropsychiatric disorders. We determined ApoE genotype frequencies and their relationship to clinical and pathological features in a diverse cohort of individuals with schizophrenia. There were no differences in ApoE genotype frequencies between schizophrenics and controls. However, the ApoE epsilon 4 genotype was associated with a younger age of onset of schizophrenia, and in an elderly subsample, individuals with the epsilon 4 allele more frequently exhibited co-existent dementia and had more neurofibrillary pathology (although none of the cases met criteria for Alzheimer's disease). This examination of ApoE in relation to clinical and neurobiological features of schizophrenia suggests that it modifies the phenotypic expression of the disease.

Adult↗
PubMed1997

Sucrose consumption in mice: major influence of two genetic loci affecting peripheral sensory responses.

Individual variability in sucrose consumption is prominent in humans and other species. To investigate the genetic contribution to this complex behavior, we conducted behavioral, electrophysiological, and genetic studies, using male progeny of two inbred mouse strains (C57BL/6ByJ [B6] and 129/J [129]) and their F2 hybrids. Two loci on Chromosome (Chr) 4 were responsible for over 50% of the genetic variability in sucrose intake. These loci apparently modulated intake by altering peripheral neural responses to sucrose. One locus affected the response threshold, whereas the other affected the response magnitude. These findings suggest that the majority of difference in sucrose intake between male B6 and 129 mice is due to polymorphisms of two genes that influence receptor or peripheral nervous system activity.

Animals↗
PubMed1997

Heritable variation in food preferences and their contribution to obesity.

What an animal chooses to eat can either induce or retard the development of obesity; this review summarizes what is known about the genetic determinants of nutrient selection and its impact on obesity in humans and rodents. The selection of macronutrients in the diet appears to be, in part, heritable. Genes that mediate the consumption of sweet-tasting carbohydrate sources have been mapped and are being isolated and characterized. Excessive dietary fat intake is strongly tied to obesity, and several studies suggest that a preference for fat and the resulting obesity are partially genetically determined. Identifying genes involved in the excess consumption of dietary fat will be an important key to our understanding of the genetic disposition toward common dietary obesity.

Animals↗
PubMed1997

Familial risk ratios for extreme obesity: implications for mapping human obesity genes.

OBJECTIVE: To determine familial risk ratios for extreme obesity to aid in the design of obesity linkage studies. DESIGN: Family study of obesity. SUBJECTS: 2349 first-degree relatives (parents and siblings) of 840 probands who are members of the National Association to Advance Fat Acceptance (NAAFA) and 5851 participants of the first phase of the National Health and Nutrition Examination Survey III. METHODS: Computed age-gender standardized risk ratios (SRRs) for obesity in relatives categorized by the level of obesity in the index case (proband). MEASUREMENT: Body mass index (BMI) (kg/m2). RESULTS: The risk of extreme obesity (BMI > or = 40) in relatives of extremely obese women (BMI > or = 40) was more than five times greater than in the population; furthermore, the risk of obesity in relatives was approximately linearly associated with the degree of obesity in the proband. The risk of thinness in relatives of obese individuals was substantially lower than in the general population. CONCLUSION: Because the familial risk ratio for extreme obesity is higher than for moderate levels of obesity, the number of families required to achieve adequate statistical power in gene mapping studies of obesity can be reduced substantially by focusing on family members of extremely obese individuals (BMI > or = 40).

Adult↗
PubMed1997

A novel phenotypic pattern in X-linked inheritance: craniofrontonasal syndrome maps to Xp22.

Craniofrontonasal syndrome (CFNS, OMIM 304110) is a distinctive genetic disorder whose main clinical manifestations include coronal synostosis, widely spaced eyes, clefting of the nasal tip and various skeletal anomalies. CFNS originally was thought to be transmitted as an autosomal dominant trait, but recent studies suggest that it is X-linked dominant, whereby all daughters of males are affected, whereas none of their sons are affected. Here we report data confirming that CFNS is X-linked, mapping to a 13 cM interval in Xp22 with a maximum two-point lod score of 3.9 (theta = 0) at DXS8022 and a multipoint lod score of 5.08 at DXS1224. Detailed phenotypic analysis shows that females are more severely affected than males, a highly unusual characteristic for an X-linked disorder. CFNS represents the first multiple congenital anomaly syndrome with this unusual phenotypic pattern of X-linked inheritance.

Chromosome Mapping↗
PubMed1996

Intake of ethanol, sodium chloride, sucrose, citric acid, and quinine hydrochloride solutions by mice: a genetic analysis.

Mice of the 129/J (129) and C57BL/6ByJ (B6) strains and their reciprocal F1 and F2 hybrids were offered solutions of ethanol, sucrose, citric acid, quinine hydrochloride, and NaCl in two-bottle choice tests. Consistent with earlier work, the B6 mice drank more ethanol, sucrose, citric acid, and quinine hydrochloride solution and less NaCl solution than did 129 mice. Analyses of each generation's means and distributions showed that intakes of ethanol, quinine, sucrose, and NaCl were influenced by a few genes. The mode of inheritance was additive in the case of ethanol and quinine, for sucrose the genotype of the 129 strain was recessive, and for NaCl it was dominant. Citric acid intake appeared to be influenced by many genes with small effects, with the 129 genotype dominant. Correlations of sucrose consumption with ethanol and citric acid consumption were found among mice of the F2 generation, and the genetically determined component of these correlations was stronger than the component related to environmental factors. The genetically determined correlation between sucrose and ethanol intakes is consistent with the hypothesis that the higher ethanol intake by B6 mice depends, in part, on higher hedonic attractiveness of its sweet taste component.

Alcohol Drinking↗
PubMed1996

A method of gap and field size determination for abutting a treatment field to a previously treated area.

A simple method of determining the new field size and the skin gap needed when abutting to a previously treated (or simulated) field is presented. The more complex case of abutting a treatment field between two previously treated fields and determining the new field length and the skin gap at each end is also addressed. Both methods utilize a single measurement on the patient's skin and the commonly used gap formula based on similar triangles. Both methods easily lend themselves to implementation through a simple BASIC program which eases any difficulties in calculation encountered during simulation.

Algorithms↗
PubMed1996

Extreme obesity may be linked to markers flanking the human OB gene.

Mice with mutations of the ob gene are extremely obese, and the human homologue (OB) has been cloned and physically mapped. The protein product of the ob gene (leptin) reduces body fat in mice when given exogenously, and leptin has been proposed to provide a lipostatic signal that regulates adiposity. Variation in the OB gene may be one genetically determined cause of obesity in human populations. To test this hypothesis, we genotyped siblings from 78 families at markers flanking the human OB gene. Pairs of siblings with extreme obesity (BMI > or = 40; n = 59) shared haplotypes identical-by-descent for the region containing the OB gene at greater than chance levels (corrected P = 0.04). Furthermore, one haplotype containing the OB gene was transmitted by heterozygous parents to extremely obese (BMI > or = 40) offspring more frequently than expected by chance, indicting significant allelic disequilibrium (corrected P = 0.027). One explanation for these linkage findings is that some individuals with extreme obesity have an allelic variant of the OB gene, although other nearby genes could contribute to obesity in these families.

Adipose Tissue↗
PubMed1996

Within birth cohort segregation analyses support recessive inheritance of body mass index in white and African-American families.

OBJECTIVE: We conducted segregation analyses of body mass index within birth cohort to determine whether previously reported support for recessive major gene inheritance in white and African-American families could have been due to higher rates of obesity in offspring than in parents, which are caused by temporal increases in obesity in recent decades. DESIGN: Segregation analysis of family data. MEASUREMENT: The body mass index (BMI), adjusted for effects of gender, linear and non-linear effects of age, education and occupation of head of household, and clinic from which family was ascertained. RESULTS: Segregation analysis results support a recessive mode of major gene inheritance of body mass index, even though we restricted our analysis to siblings born within the same post-1945 cohort. We also found support for substantial polygenic heritability of body mass index, which is consistent with a multigenic heritability. There was no significant heterogeneity between white and African-American families in support for a recessive mixed model. However, some differences in particular parameters were found, with higher gene frequency, lower polygenic heritability and a larger variance associated with the major gene model in African-Americans. CONCLUSION: Our present segregation analysis shows that the recessive pattern, whether due to single or multiple genes, cannot be explained by inter-generational differences in obesity prevalence or family correlation. There was suggestive evidence of a higher major gene frequency and larger gene effect size in African-American families.

Black People↗
PubMed1995

Segregation analysis of human red blood cell thiopurine methyltransferase activity.

Thiopurine methyltransferase (TPMT) catalyzes thiopurine S-methylation, an important metabolic pathway for drugs such as 6-mercaptopurine (6-MP). Inherited differences in the activity of this enzyme are related to individual differences in the therapeutic efficacy and toxicity of 6-MP and other thiopurine drugs. Variation of TPMT activity in the red blood cell (RBC) has been found to reflect activity differences in less accessible tissues. Previously reported qualitative analyses of inheritance of RBC TPMT in families suggested that a major gene plays a role in the regulation of activity of this enzyme. In the present study we completed complex segregation analyses of RBC TPMT activity of 213 individuals in 49 families that were randomly ascertained through children in the Rochester, MN, public school system. We found clear evidence of a major gene effect on RBC TPMT activity. Both transformed and untransformed data supported the segregation of a Mendelian major gene with frequency of 0.94 for the allele conferring high enzyme activity. The genotype distributions of individuals who were homozygous for the low activity allele, heterozygous, and homozygous for the high activity allele accounted for approximately 0.3%, 11.2%, and 88.5%, respectively, of the individuals in the sample. This major locus accounted for 66% of the total variance in untransformed RBC TPMT activity. Although there were significant residual family correlations among probable high activity homozygotes, there was insufficient power to detect additional major locus or polygenic inheritance effects on the residual variance.

Adolescent↗
PubMed1995

Absence of linkage between human obesity and the mouse agouti homologous region (20q11.2) or other markers spanning chromosome 20q.

Mutant alleles of the agouti gene cause obesity in the mouse and the homologous gene in humans has been mapped to chromosome 20q11.2. An allelic variant of the agouti gene could account for obesity in humans and we tested this hypothesis by genotyping 210 sibling pairs from 45 families segregating an obesity phenotype. Using sibling pair linear regression analysis, evidence for linkage between obesity and markers flanking the agouti locus and other markers spanning chromosome 20q was assessed. We found no correlation between identity-by-descent at these markers and obesity differences within pairs. In the mouse, obesity caused by mutations of the agouti gene develops later in life, so a subset of families with adult-onset obesity were also tested for linkage, with negative results. Although it is not possible to exclude alleles of the agouti gene as a contributor to obesity in humans, the absence of positive linkage in this study suggests that either the agouti gene has small effects or the allele frequency is low.

Age of Onset↗
PubMed1995

Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2.

Opitz syndrome (OS, McKusick 145410) is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome, and G syndrome. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports suggested that OS was inherited as an autosomal dominant trait. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.

Abnormalities, Multiple↗
PubMed1995

Propylthiouracil tasting: determination of underlying threshold distributions using maximum likelihood.

The ability to taste low concentrations of propylthiouracil (PROP) and related bitter compounds is heritable. The current analysis determines whether the distribution of PROP taste thresholds is consistent with an additive or a dominant mode of Mendelian transmission. To that end, the lowest concentration of PROP detectable was determined for 1015 subjects and models of bi- or tri-modal distributions of PROP taste thresholds were tested. The model with the greatest likelihood had three distributions and followed an additive model of PROP taste sensitivity if the variances associated with the distributions were assumed to be equal. However, if the taste thresholds were transformed to remove skewness, or if the variances were unequal, then three- or two-distribution models were equally likely. Resolution of the mode of inheritance for bitter taste perception awaits additional family studies and the characterization of the molecular basis of taste perception for these bitter compounds.

Adolescent↗
PubMed1995

Human obesity does not segregate with the chromosomal regions of Prader-Willi, Bardet-Biedl, Cohen, Borjeson or Wilson-Turner syndromes.

Prader-Willi, Bardet-Biedl, Cohen, Borjeson and Wilson-Turner syndromes are genetic disorders characterized by obesity and other diverse abnormalities. These disorders have been mapped to their respective chromosomal regions, and we hypothesize that each region contains a gene or genes important in the regulation of body weight. We tested this hypothesis by genotyping sibling pairs (n = 207; 17 markers) from 44 families who were segregating an extreme obesity phenotype but were otherwise clinically normal. The number of alleles shared between siblings from these chromosomal regions did not correlate with similarity in body mass index (kg/m2). If genes in these regions contribute to non-syndromal obesity, the prevalence is low and the corresponding alleles are rare.

Adult↗
PubMed1994

Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers.

OBJECTIVE: To determine whether schizophrenics and their nonschizophrenic siblings have a similar pattern of neuropsychological deficit when compared with normal controls. DESIGN AND PARTICIPANTS: Fifteen probands with schizophrenia, 16 of their nonschizophrenic siblings, and 31 unrelated, demographically balanced, normal individuals underwent evaluation with a comprehensive neuropsychological test battery. All subjects were screened for history of head injury, neurologic illness, major medical conditions, substance use, and axis I psychiatric disorders other than schizophrenia. Probands underwent evaluation twice: once at intake when half had never received neuroleptic medication and the other half had received none for a minimum of 2 weeks, and again at the 2- to 4-week follow-up, after stabilization with neuroleptic medications. RESULTS: Both schizophrenics and their nonschizophrenic siblings were impaired neuropsychologically compared with normal controls, with the nonschizophrenic siblings' performance intermediate between that of the schizophrenic siblings and the normal controls on all measures of functioning. The shapes of the deficit profiles of schizophrenic patients and their siblings were similar; in patients, verbal memory, abstraction, attention, and language functions were significantly more affected compared with spatial abilities, spatial memory, and sensory-motor functions, with a nonsignificant trend in the same direction in siblings. Cognitive functioning in patients was found to be stable across changes in medication status and clinical state. Four fifths of patients obtained more deviant scores than their nonschizophrenic siblings. Among the sibling group, those with probable and certain diagnoses of schizotypal personality disorder were more impaired compared with those without schizophrenia-spectrum symptoms. CONCLUSION: These results support the hypothesis that impaired information processing aggregates in the family members of schizophrenics and may serve as an indicator of genetic vulnerability to the disorder. Further work is needed to establish whether particular areas of functioning are selectively impaired in relatives and to determine whether the performance deficits are mediated by structural and/or metabolic disturbances in specific brain regions.

Adult↗
PubMed1994

Genetics of dietary obesity in AKR/J x SWR/J mice: segregation of the trait and identification of a linked locus on chromosome 4.

We describe a new multiple gene mouse model of differential sensitivity to dietary obesity that provides a tool for dissecting the genetic basis for body composition and obesity. AKR/J and SWR/J male mice, as well as male progeny of intercrosses between these strains, were fed a high-fat diet for 12 weeks beginning at 5 weeks of age. Body weight and energy intake were assessed weekly. At the conclusion of the dietary manipulation, an adiposity index was calculated by dividing the weight of seven dissected adipose depots by the carcass weight. AKR/J mice had approximately sixfold greater adiposity than SWR/J mice. Examination of the segregation of the adiposity trait in the progeny of crosses between these strains indicates that the trait is determined by a minimum of one to four genetic loci and that there is significant dominance of the AKR/J genotype. A preliminary analysis with markers linked to the known mouse obesity genes ob, db, tub, and fat showed no linkage with these loci. However, a quantitative trait locus was found that maps distal to the db gene on Chromosome (Chr) 4. This locus has been designated dietary obese 1 or Do1.

Alleles↗
PubMed1994

The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members.

Members of the National Depressive and Manic-Depressive Association who have bipolar disorder were surveyed. 59% of respondents had their first symptoms during childhood or adolescence. Long delays between symptom onset, treatment-seeking, and receipt of a bipolar diagnosis were common. 45% of respondents currently experience frequent recurrences. Child/adolescent onset was associated with a positive family history, depressive or mixed initial symptoms, and frequent recurrence, with predominantly depressive symptoms. Frequent recurrences were associated with depressive or mixed initial symptoms and depressive episodes, but not with medication non-compliance. Both child/adolescent onset and frequent recurrence were associated with increased social morbidity, which was diminished by effective treatment. Respondents with frequent recurrences were less likely to be treated with mood-stabilizers, more likely to be treated with anti-depressants, or anxiolytics, and more likely to report past anxiety symptoms and diagnoses. 13% of respondents had no medical insurance, and 15% had failed to take medicine for financial reasons. The treatment of bipolar illness could be enhanced by (a) public health efforts to promote early diagnosis and treatment; (b) ensuring adequate trials of mood-stabilizers for patients with frequent recurrences; (c) further research on bipolar disorder with prominent anxiety symptoms; and (c) improved access to mental health care.

Adolescent↗