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Biomedical subjects

A S Deinard

Publications and source records attributed to A S Deinard.

At least 19 recordsLinked to original sources
PubMed2000

Short tandem-repeat polymorphism/alu haplotype variation at the PLAT locus: implications for modern human origins.

Two dinucleotide short tandem-repeat polymorphisms (STRPs) and a polymorphic Alu element spanning a 22-kb region of the PLAT locus on chromosome 8p12-q11.2 were typed in 1,287-1,420 individuals originating from 30 geographically diverse human populations, as well as in 29 great apes. These data were analyzed as haplotypes consisting of each of the dinucleotide repeats and the flanking Alu insertion/deletion polymorphism. The global pattern of STRP/Alu haplotype variation and linkage disequilibrium (LD) is informative for the reconstruction of human evolutionary history. Sub-Saharan African populations have high levels of haplotype diversity within and between populations, relative to non-Africans, and have highly divergent patterns of LD. Non-African populations have both a subset of the haplotype diversity present in Africa and a distinct pattern of LD. The pattern of haplotype variation and LD observed at the PLAT locus suggests a recent common ancestry of non-African populations, from a small population originating in eastern Africa. These data indicate that, throughout much of modern human history, sub-Saharan Africa has maintained both a large effective population size and a high level of population substructure. Additionally, Papua New Guinean and Micronesian populations have rare haplotypes observed otherwise only in African populations, suggesting ancient gene flow from Africa into Papua New Guinea, as well as gene flow between Melanesian and Micronesian populations.

Africa South of the Sahara↗
PubMed2000

Identifying conservation units within captive chimpanzee populations.

One of the primary objectives in the captive management of any endangered primate is to preserve as much as possible the genetic diversity that has evolved and still exists in wild gene pools. The rationale for this is based on the theoretical understanding of the relationship between genetic diversity and fitness in response to selection. There remains little consensus, however, as to the type of genetic data that should be used to monitor captive populations. In order to develop a deeper understanding of the degree and nature of genetic diversity among "wild" chimpanzee gene pools, as well as to determine if one type of genetic data is more useful than others, DNA sequence data were generated at three unlinked, nonrepetitive nuclear loci, one polymorphic microsatellite, and the mitochondrial D-loop for 59 unrelated common and pygmy chimpanzees. The results suggest that: 1) data from nuclear loci can be used to differentiate common chimpanzee subspecies; 2) pygmy chimpanzees may have less genetic diversity than common chimpanzees; 3) shared microsatellite alleles do not always indicate identity by descent; and 4) nonrepetitive loci provide unique insights into evolutionary relationships and provide useful information for captive management programs.

Animals↗
PubMed1999

Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans.

BACKGROUND: Endogenous retroviruses contribute to the evolution of the host genome and can be associated with disease. Human endogenous retrovirus K (HERV-K) is related to the mouse mammary tumor virus and is present in the genomes of humans, apes and cercopithecoids (Old World monkeys). It is unknown how long ago in primate evolution the full-length HERV-K proviruses that are in the human genome today were formed. RESULTS: Ten full-length HERV-K proviruses were cloned from the human genome. Using provirus-specific probes, eight of the ten were found to be present in a genetically diverse set of humans but not in other extant hominoids. Intact preintegration sites for each of these eight proviruses were present in the apes. A ninth provirus was detected in the human, chimpanzee, bonobo and gorilla genomes, but not in the orang-utan genome. The tenth was found only in humans, chimpanzees and bonobos. Complete sequencing of six of the human-specific proviruses showed that full-length open reading frames for the retroviral protein precursors Gag-Pro-Pol or Env were each present in multiple proviruses. CONCLUSIONS: At least eight full-length HERV-K genomes that are in the human germline today integrated after humans diverged from chimpanzees. All of the viral open reading frames and cis-acting sequences necessary for HERV-K replication must have been intact during the recent time when these proviruses formed. Multiple full-length open reading frames for all HERV-K proteins are present in the human genome today.

Animals↗
PubMed1998

A global haplotype analysis of the myotonic dystrophy locus: implications for the evolution of modern humans and for the origin of myotonic dystrophy mutations.

Haplotypes consisting of the (CTG)n repeat, as well as several flanking markers at the myotonic dystrophy (DM) locus, were analyzed in normal individuals from 25 human populations (5 African, 2 Middle Eastern, 3 European, 6 East Asian, 3 Pacific/Australo-Melanesian, and 6 Amerindian) and in five nonhuman primate species. Non-African populations have a subset of the haplotype diversity present in Africa, as well as a shared pattern of allelic association. (CTG)18-35 alleles (large normal) were observed only in northeastern African and non-African populations and exhibit strong linkage disequilibrium with three markers flanking the (CTG)n repeat. The pattern of haplotype diversity and linkage disequilibrium observed supports a recent African-origin model of modern human evolution and suggests that the original mutation event that gave rise to DM-causing alleles arose in a population ancestral to non-Africans prior to migration of modern humans out of Africa.

Alleles↗
PubMed1998

Evolution of a D2 dopamine receptor intron within the great apes and humans.

Although direct DNA sequencing may allow rapid and high quality comparative phylogenetic analyses among species, such an approach may not be the most efficient method by which to make a large number of cross-species comparisons. We illustrate the use of Denaturing Gradient Gel Electrophoresis (DGGE) to screen a D2 Dopamine Receptor intron for DNA sequence variation, both within and between closely related species, in order to infer their evolutionary relationships. Our results suggest that: a) humans have less genetic variation than the great apes; b) pygmy chimpanzees have less genetic variation than common chimpanzees; and c) DNA sequence comparative analyses of primates require adequate sampling, both in number and in geographical range.

Animals↗
PubMed1998

Analyses of cross species polymerase chain reaction products to infer the ancestral state of human polymorphisms.

In numerous population genetic and disease association studies decisions about the ancestry of polymorphic alleles are often made based on the relative frequency of the alleles in the extant populations with the most frequent allele being deemed as ancestral. However, the frequency of an allele in a population is generally not a perfect indicator of its ancestral status. A more accurate method to assess ancestral/derived status of polymorphic alleles involves identification of shared alleles between species. We used this strategy to examine genomic regions homologous to several human polymorphisms in four species of non-human primates. Cross species polymerase chain reaction (CS-PCR), with primers designed from human sequence, was used to investigate regions of interest. Nineteen polymorphisms at six loci (DRD2, HOXB@, PAH, D4S10, RBP3, and RET) were examined either by restriction fragment length analysis of PCR products (PCR-RFLP) or by direct sequencing. At seventeen of the eighteen PCR-RFLPs, non-human primates were monomorphic and identical to each other for either lack of restriction enzyme site or presence of the site. Thus, at these seventeen polymorphic sites the shared alleles are most likely to be the ancestral ones in humans. In several cases we have used sequence data to further demonstrate that the nucleotide at the site of the polymorphism is conserved between species confirming the hypothesis of a single ancestral allele. However, not all human alleles can be simply resolved into ancestral and derived; sequence data from one PCR-RFLP (in an intron of the PAH locus) and a single strand conformational polymorphism (SSCP) in the 3' untranslated region (UTR) of the DRD2 gene illustrate this point.

Alleles↗
PubMed1997

Survey of maximum CTG/CAG repeat lengths in humans and non-human primates: total genome scan in populations using the Repeat Expansion Detection method.

Repeat Expansion Detection (RED) is an efficient and simple method for detecting repeat expansions in the human genome, including expansion mutations resulting in disease. Here we report the first population survey of CTG/CAG repeat lengths in humans using the RED method; we have determined maximum CTG/CAG repeat length in 244 individuals from six human populations: Danes, Chinese, Japanese, Rondonian Surui, Maya and Mbuti/Biaka Pygmies. We have also sampled a number of non-human primates including eight orang-utans (Pongo pygmaeus), seven gorillas (Gorilla gorilla), seven pygmy chimpanzees (Pan paniscus), 13 common chimpanzees (Pan troglodytes) and three Hylobatidae (one Hylobates lar, one H.klossii, and one H.syndactylus). Our results demonstrate the existence of significant variation in the sizes and frequencies of the longest CTG/CAG repeat length seen per individual both within and between human populations. The population differences argue that overall mutation rates at CTG/CAG repeat loci are sufficiently low that mutation does not obliterate the effect of random genetic drift and clearly indicate that population stratification could occur in disease association studies using the RED method. No significant differences were detected among the non-human primates sampled. Our results also show that both common chimpanzees and pygmy chimpanzees (bonobos) are polymorphic for maximum length of any CTG/CAG repeats while no variation was found for gorillas and orang-utans.

Animals↗
PubMed1996

Conserved regulatory element involved in the early onset of Hoxb6 gene expression.

We have identified a 338 bp DNA fragment, the lateral plate mesoderm (LPM) enhancer, that is highly conserved between mouse and human. The LPM enhancer directs gene expression into the posterior lateral plate mesoderm and hindgut endoderm at early stages of development. By reporter gene analysis in transgenic mice, we demonstrate that both mouse and human DNA sequences possess similar enhancer activity. The expression patterns of the transgene and Hoxb6 during early stages of mouse development are identical, suggesting that the LPM enhancer is involved in the initial activation of Hoxb6 gene expression in posterior regions of mammalian embryos.

Animals↗
PubMed1995

Sociocultural factors in the use of prenatal care by Hmong women, Minneapolis.

Understanding the sociocultural context of prenatal care underuse by an immigrant population can suggest programmatic changes that result in more effective health care delivery. Ethnographic survey interviews of female Hmong clinic patients conducted in 1987/88 revealed that they objected to biomedical procedures and to being attended by several doctors; the women also reported poor communication with staff as a problem. Clinic reforms implemented in 1989/90 included hiring a nurse-midwife, reducing the number of pelvic examinations, expanding hours of operation, creating a direct telephone line to Hmong interpreters, and producing a Hmong-language prenatal health care education videotape. Women interviewed in 1993 reported a more positive clinic experience.

Adult↗
PubMed1995

Evolution of haplotypes at the DRD2 locus.

We present here the first evolutionary perspective on haplotypes at DRD2, the locus for the dopamine D2 receptor. The dopamine D2 receptor plays a critical role in the functioning of many neural circuits in the human brain. If functionally relevant variation at the DRD2 locus exists, understanding the evolution of haplotypes on the basis of polymorphic sites encompassing the gene should provide a powerful framework for identifying that variation. Three DRD2 polymorphisms (TaqI "A" and "B" RFLPs and the (CA)n short tandem repeat polymorphic in all the populations studied, and they display strong and significant linkage disequilibria with each other. The common haplotypes for the two TaqI RFLPs are separately derived from the ancestral haplotype but predate the spread of modern humans around the world. The knowledge of how the various haplotypes have evolved, the allele frequencies of the haplotypes in human populations, and the physical relationships of the polymorphisms to each other and to the functional parts of the gene should now allow proper design and interpretation of association studies.

Base Sequence↗
PubMed1994

Detection of DNA sequence variation via deliberate heteroduplex formation from genomic DNAs amplified en masse in "population tubes".

We have developed the population tube (poptube) system for sensitive detection and large-scale sampling of DNA sequence variation in several human populations of wide geographic distribution. In this methodology, genomic DNAs from five individuals in a population are PCR amplified en masse to maximize deliberately the chances of forming heteroduplexes among allelic variants. Interpopulation mixing is performed in a separate set of tubes containing one individual from each of five populations as well as a reference chimpanzee sample deliberately chosen to be different from all humans. Mismatches at sites of allelic variation retard the electrophoresis and reduce the stability of heteroduplex molecules. The products are electrophoresed on denaturing gradient gels where detection of heteroduplexes is accomplished readily. Using poptubes, we have discovered a rare variant in an otherwise highly conserved 440-bp segment in the long intron of the glucose-6-phosphate dehydrogenase (G6PD) gene. The polymorphism at this X-chromosome locus could be only detected in males by mixing samples, as homoduplexes for both alleles co-focus on denaturing gradient electrophoresis.

Animals↗
PubMed1992

Lead levels among pregnant women in Hennepin County.

The purpose of this study was to determine the blood lead levels (Pb-B) of urban pregnant women with low incomes and/or living in areas with heavily traveled roads, dilapidated housing, and industrial plants. We measured blood lead in 1,055 pregnant Minneapolis-area women at entry to prenatal care and in one-third of the sample during the second half of pregnancy. The mean Pb-B level of the first sample (n = 1,055) was 1.83 +/- 1.83 micrograms/dL; of the second sample (n = 375), 1.99 +/- 1.92 micrograms/dL. Only one woman had a Pb-B level greater than 12.0 micrograms/dL, which was the result of occupational exposure. The low lead levels found in this study indicate that it is not necessary to routinely screen pregnant women for elevated Pb-B levels in our geographic area. Rather, women should be screened via an environmental questionnaire to ascertain the risk of lead exposure.

Adolescent↗
PubMed1986

1% permethrin cream rinse vs 1% lindane shampoo in treating pediculosis capitis.

The therapeutic efficacy and tolerance of a single application of 1% permethrin cream rinse, applied for ten minutes, and a single application of 1% lindane shampoo applied, as recommended by the manufacturer, for four minutes, against the head louse Pediculus humanus var capitis were compared in a single-blinded, randomized, controlled clinical trial. Of 573 patients enrolled at eight centers, 559 were assessable for tolerance and 508 for efficacy. Of the 257 patients treated with 1% permethrin cream rinse, 99% were lice free at 14 days; of the 251 patients treated with 1% lindane shampoo, 85% were lice free at 14 days. The difference is statistically significant. For both treatments, adverse experiences were infrequent, mild, and usually difficult to distinguish from the symptoms of head lice infestation. A single ten-minute application of 1% permethrin cream rinse was well tolerated, highly effective, and therapeutically superior to a single four-minute application of 1% lindane shampoo.

Clinical Trials as Topic↗
PubMed1986

Cognitive deficits in iron-deficient and iron-deficient anemic children.

Eighteen- to 60-month-old iron-deficient anemic children given iron therapy (n = 25) and a control group matched for mother's educational level showed no significant difference in mean mental development score at baseline. The control group's mean score was increased significantly over baseline score at 3 and 6 months and was significantly higher than the experimental group's mean score at 3 months. Although the experimental group demonstrated hematologic correction over 6 months, mean mental development score showed no significant improvement. Scores for an iron deficient not anemic group given iron (n = 22), despite complete hematologic correction over the six months of observation, and for its control group, did not change significantly. Baseline scores for an iron-deficient not anemic placebo group (n = 23) and for its control group were not significantly different. At 3 months the control group score had increased significantly, whereas that for the experimental group had not. When experimental and control subjects were matched on baseline mental development score, the control subjects experienced increases in scores over time, further confirming an impaired ability to improve scores with repeated testing in the experimental groups. Behavioral rating data (responsiveness to examiner, responsiveness to environment, and emotional tone) revealed significant differences between the iron-deficient anemic group and its control group at 3 and 6 months, with the control group rated more responsive, suggesting that iron deficiency, alone or in association with anemia, may have some lasting effect on behavior and development. Group differences were also found between the mean number of occurrences of multiple stressful events. Failure to show improvement in scores in the iron-deficient anemic group may reflect the fact that those children were less testable than were children in the control group, despite repeated testings, a theory supported by the infant behavior rating data. This may be related to some irreversible behavioral deficit or to an adverse environmental milieu (e.g., stress).

Anemia, Hypochromic↗
PubMed1985

Iron deficiency among incarcerated juvenile delinquents.

A population of 163 incarcerated delinquents (126 males and 37 females aged 12-18 years) was studied to determine the prevalence of iron deficiency and to compare hemoglobin (Hgb), mean corpuscular volume (MCV), serum ferritin (SF), and erythrocyte protoporphyrin/hemoglobin (EP/Hgb) as predictors of response to iron therapy. Thirty-two percent of females and 6% of males had SF less than or equal to 12 ng/ml; 51% of females and 24% of males had SF less than or equal to 20 ng/ml. The mean SF was 17.7 ng/ml for females and 29.2 ng/ml for males. Of the 163 subjects, 53 were at risk for iron deficiency based on SF, Hgb, EP/Hgb, or MCV criteria. Twenty-one completed treatment with iron, and nine had greater than 1 g rise in Hgb. The following tests identified responders: SF less than or equal to 12 ng/ml-5/9; SF less than or equal to 20 ng/ml-9/9; Hgb less than or equal to third percentile-4/9; Hgb less than or equal to tenth percentile-7/9; MCV less than or equal to tenth percentile-2/9; EP/Hgb greater than or equal to 3.0 micrograms/g Hgb-2/9; EP/Hgb greater than or equal to 2.5 micrograms/g Hgb-4/9. Serum ferritin less than or equal to 20 ng/ml had a false positive rate of 57%; Hgb less than or equal to tenth percentile and EP/Hgb greater than or equal to 2.5 mu g/g Hgb had no false positives. The significance of the high prevalence of iron deficiency among a population of incarcerated adolescents is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗