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PubMed2026

Large-scale admixture mapping in the All of Us Research Program improves the characterization of cross-population phenotypic differences.

Admixed individuals have been understudied in medical research largely due to their complex genetic ancestries. However, the consideration of admixture can identify ancestry-enriched genetic associations, delineating genetic underpinnings of cross-population phenotypic variation. Here, we performed admixture mapping in individuals with inferred admixture from African and European populations (N = 48,921). Across 22 traits, we identified 71 ancestry-trait associations, including loci where ancestral haplotypes explained phenotypic variation yet were missed by single-variant association testing due to their stricter multiple testing burden. One such locus where inferred local AFR ancestries are associated with increased hemoglobin A1c (HbA1c) was 12q14.3, highlighting its potential role in explaining differences between populations. Together, our results expand upon the phenotypic differences between populations and characterize loci where genetic ancestries play a critical role in the architecture of disease.

Humans↗
PubMed2000

Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study.

It has been suggested that genetic variation in the angiotensin-converting enzyme (ACE) gene is associated with physical performance. We studied the association between the ACE insertion (I)/deletion (D) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian (n = 476) and black (n = 248) subjects. Phenotypes measured were oxygen uptake (VO(2)), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximal VO(2) (VO(2 max))] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60% VO(2 max)). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant (P values from 0.042 to 0. 0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14-38% greater increase with training in VO(2 max), VO(2) at 80% of VO(2 max), and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.

Adult↗
PubMed1980

Prenatal chromosomal diagnosis. Racial and geographic variation for older women in Georgia.

In a study of Georgia women aged 40 years and older, 15% made use of prenatal chromosomal diagnosis. There was, however, substantial racial and geographic variation, ranging from a use ratio of 60% among whites in two large urban counties to 0.5% among blacks outside Augusta and Atlanta health districts. This simple population-based epidemiologic analysis suggests that future program planning for genetic services in Georgia should address ways to increase access by rural women, especially blacks. Similar analyses in other states could be used for planning genetic services.

Abortion, Therapeutic↗
PubMed2005

Biofortifying crops with essential mineral elements.

Humans require more than 22 mineral elements, which can all be supplied by an appropriate diet. However, the diets of populations subsisting on cereals, or inhabiting regions where soil mineral imbalances occur, often lack Fe, Zn, Ca, Mg, Cu, I or Se. Traditional strategies to deliver these minerals to susceptible populations have relied on supplementation or food fortification programs. Unfortunately, these interventions have not always been successful. An alternative solution is to increase mineral concentrations in edible crops. This is termed 'biofortification'. It can be achieved by mineral fertilization or plant breeding. There is considerable genetic variation in crop species that can be harnessed for sustainable biofortification strategies. Varieties with increased mineral concentrations in their edible portions are already available, and new genotypes with higher mineral densities are being developed.

Crops, Agricultural↗
PubMed2006

Review of quantitative trait loci identified in the chicken.

Methods for mapping QTL are actively used in the chicken to identify chromosomal regions contributing to variation in traits related to growth, disease resistance, egg production, behavior, and metabolic parameters. However, higher-resolution mapping and better knowledge of the genetic architecture underlying QTL are needed for successful application of this information into breeding programs. Therefore, this paper summarizes and integrates original, primary QTL studies in the chicken to identify basic information on the genetic architecture of quantitative traits in chickens. The results of this review show several instances of consensus of QTL locations for similar traits from independent studies. Furthermore, the consensus of QTL location for different traits and evidence for QTL with parent-of-origin effect, transgressive alleles, epistatic QTL, and QTL x sex interaction in chicken are presented and discussed. This information can be helpful in identifying genes or mutations underlying the QTL and in the application of genomic information in marker-assisted breeding programs.

Animals↗
PubMed1999

Genetic characterization of two Eragrostis species using AFLP and morphological traits.

Tef [Eragrostis tef (Zucc.) Trotter] is the most important cereal crop in Ethiopia. An experiment was conducted to investigate genetic diversity among four cultivars of tef and 14 accessions of Eragrostis pilosa using radiolabelled and silver stained amplified fragment length polymorphism. Morphological traits were also evaluated. A total of 897 markers were obtained out of which 395 were polymorphic using 11 primer combinations. Cluster analysis revealed accessions of E. pilosa which are distantly related and others closely related to tef. Our previous experience also indicates that E. pilosa is crossable with tef. Those accessions distantly related to tef could be used in a crossing program to generate a population for selection and/or genetic mapping. Such genetic mapping populations will form an important entry point towards the molecular genetic dissection of the plant genus, Eragrostis, especially in the context of comparative mapping. Knowledge gained from such study, apart from tef improvement, will also be useful for many forage and turf grass species where little molecular genetic information is available. Nine cultivars or accessions had one or more unique fragments using one or more AFLP primers indicating the potential of the technology in fingerprinting tef in a breeding or seed multiplication program. The results also showed that clusters obtained using silver staining and gamma 33P-ATP labeling were similar, suggesting that silver staining could be used as an alternative to radiolabeling at least in genetic diversity analysis. Significant genetic variation was obtained for morphological traits. Of particular interest to tef breeding was short plant stature in E. pilosa which could be transferred to tef to minimize the problem of lodging. Diversity revealed at the morphological trait level was not commensurate with that observed for AFLP. This was due to the small number of available morphological traits and their interaction with the environment.

Base Sequence↗
PubMed2005

Single nucleotide polymorphism in transcriptional regulatory regions and expression of environmentally responsive genes.

Single nucleotide polymorphisms (SNPs) in the human genome are DNA sequence variations that can alter an individual's response to environmental exposure. SNPs in gene coding regions can lead to changes in the biological properties of the encoded protein. In contrast, SNPs in non-coding gene regulatory regions may affect gene expression levels in an allele-specific manner, and these functional polymorphisms represent an important but relatively unexplored class of genetic variation. The main challenge in analyzing these SNPs is a lack of robust computational and experimental methods. Here, we first outline mechanisms by which genetic variation can impact gene regulation, and review recent findings in this area; then, we describe a methodology for bioinformatic discovery and functional analysis of regulatory SNPs in cis-regulatory regions using the assembled human genome sequence and databases on sequence polymorphism and gene expression. Our method integrates SNP and gene databases and uses a set of computer programs that allow us to: (1) select SNPs, from among the >9 million human SNPs in the NCBI dbSNP database, that are similar to cis-regulatory element (RE) consensus sequences; (2) map the selected dbSNP entries to the human genome assembly in order to identify polymorphic REs near gene start sites; (3) prioritize the candidate polymorphic RE containing genes by searching the existing genotype and gene expression data sets. The applicability of this system has been demonstrated through studies on p53 responsive elements and is being extended to additional pathways and environmentally responsive genes.

Databases, Genetic↗
PubMed1994

Mechanisms involved in living systems organisation, especially the programming necessary to enable the construction of individuals in three dimensions.

The complexity of the organization of living systems escalates by orders of magnitude in the development, from single precursor cells, not only of the three-dimensional structures characterizing each species but also in the variations necessary to accommodate the 1 million or more separate and identifiable species on this planet. Although the genetic information controlling such information is currently considered to reside in cellular DNA, it is also held that such information is restricted to a linear form encoding specifically for protein. However, this not only fails to explain the co-ordination of the vast number of processes occurring in simple, single cell, organisms, but also the integration of cellular activities to serve the interest of the total system. In particular how can a homeobox containing only genes encoding specifically for proteins organize and implement the mechanisms necessary for three-dimensional development? This, and the organization and implementation of the massive amount of information necessary to execute the construction of such a wide range of species, each in its own unique and exquisite detail, calls for internal programming of a highly complex and sophisticated nature. It is proposed here that such a central computer-analog program does exist, housed in the molecular electronic structure of cellular nucleic acid, primarily in DNA: its possible nature is discussed. Since precursor cells contain only of the order of 10(-10) g of DNA, this proposal involves an increase in information storage efficiency comparable with that already achieved by silicon microprocessors over mechanical calculators.

Animals↗
PubMed1997

State-to-state variations in newborn screening policies.

BACKGROUND: Population-based newborn screening for genetic and metabolic disorders is standard practice in all states in the United States. Policies governing newborn screening are determined at the state level; however, and thus, a great degree of variability exists between states regarding many facets of such screening. OBJECTIVE: To gather information relating to the processes, content, and outcomes of policy making affecting newborn screening programs across the United States. METHODS: We surveyed the directors of newborn screening programs for each of the 50 states using a postal questionnaire. The questionnaire solicited information about the specific tests incorporated in each state's panel of screening tests and information pertaining to the policy-making processes by which decisions are reached regarding this testing. RESULTS: Substantial variation exists across states regarding both the processes of policy formulation and the outcomes of decisions made about newborn screening. All states currently screen for phenylketonuria and congenital hypothyroidism. Extensive variation exists across states in testing for other disorders. The processes by which state policy makers arrive at decisions in this area are extremely diverse. Almost three fourths of the states have standing expert advisory bodies who issue recommendations regarding screening program modifications, but the authority granted to these panels varies substantially. Some regional cooperation in this area exists. CONCLUSIONS: Further development of regional cooperation could offer some states greater efficiency in both laboratory testing and screening policy formulation. From the standpoint of an individual state. Wisconsin's approach to policy development in this area is described as a model worthy of consideration.

Health Policy↗
PubMed1999

Coronary heart disease. At the interface of molecular genetics and preventive medicine.

BACKGROUND: Susceptibility to common chronic diseases such as coronary heart disease (CHD) appears to be influenced by "context-dependent effects," which include interactions among genes (genetic epistasis) and among genes and environmental factors (gene-environment interactions). METHODS: A synthesis of current knowledge and research findings demonstrates the importance of integrating genetic research on cardiovascular disease with preventive medicine and public health initiatives. RESULTS: A variety of candidate genes have been implicated in risk for CHD, but only limited examples of context-dependent effects have been described. Interactions between genetic and environmental factors appear to influence lipid metabolism, plasma homocysteine levels, and pharmacologic response to many commonly prescribed medications. Quantification of genetic effects associated with increased disease risk that are modifiable by interventions such as diet, exercise, and smoking cessation is an important interface between molecular genetics and preventive medicine. CONCLUSIONS: As a primary focus of preventive medicine expands to encompass early detection and treatment of asymptomatic individuals at risk for disease, the ability to quantify the influence of context-dependent effects on disease risk will be critical for determining drug safety and effectiveness in diverse patient populations and for implementing effective prevention and treatment programs.

Coronary Disease↗
PubMed2002

The variability of the mitochondrial genome in human aging: a key for life and death?

The impressive performance of the research in mitochondrial genetics and human aging in the last decade outlines a new scenery in which the inherited variation of the mitochondrial genome (mtDNA) may play a role in rate and quality of aging. This variation in humans was initially looked at as nearly neutral, and useful just for the reconstruction of human population history. However, recent data suggest that different mtDNA molecules are qualitatively different from each other. The aim of this paper is to discuss current ideas on the relationships among mitochondrial function, mtDNA inherited variation, and aging. The main processes where the mitochondrion is involved and the importance these processes have on aging and death of individuals will be described. A possible connection between programmed death phenomena (mitoptosis, apoptosis, phenoptosis) and rate and quality of aging will be discussed. Finally, the possible role played in these processes by the mtDNA germline variation will be explored.

Aging↗
PubMed1992

Potential contribution of cryopreserved germ plasm to the preservation of genetic diversity and conservation of endangered species in captivity.

Demographic and genetic objectives of captive propagation programs for endangered species focus on establishing demographically secure populations that maintain adequate levels of genetic diversity. Long-term storage and utilization of cryopreserved germ plasm could extend the population's generation length and allow higher levels of genetic variation to be maintained in smaller populations. Since fewer breeding animals would be needed, more species would be "rescued" from extinction using the cage facilities currently available at existing institutions. Doubling generation lengths for callitrichid primates through use of cryopreservation could almost triple the number of species that could be rescued in world zoos. Additionally, long-term cryopreservation would allow for a third population, that of the frozen zoo. Three-way exchange of germ from germ plasm banks to captive and wild populations would increase genetic diversity at reduced risk and expense. Advances in reproductive technology and better understanding of the reproductive physiology of these animal populations are necessary to permit routine application of artificial insemination and embryo transfer using frozen-stored germ plasm.

Animals↗
PubMed1994

Poultry immunogenetics: which way do we go?

A major goal in poultry immunogenetics is the enhancement of innate immunoresponsiveness and resistance to disease. This may be pursued by studying either single genes or polygenic traits. The MHC is perhaps the best-characterized family of host genes that modulates response to a variety of antigens and pathogenic challenges. The association of different MHC alleles with disease resistance has been known for decades. But only recently has analysis at the DNA level opened new avenues of understanding and new opportunities for application of genetic variation in the MHC with immunoresponsiveness. An alternate approach to molecular analysis is selection for a desired phenotype controlled by polygenes. Several studies have illustrated the successful alteration of immunoresponsiveness by genetic selection for antibody production. Recently, a selection program based upon multiple traits of immune response was conducted. Results of this project demonstrated that selection on multiple immune-response traits altered immunophysiology, MHC allelic frequencies, and disease resistance. Several areas for future pursuits in poultry immunogenetics research are proposed.

Animal Husbandry↗
PubMed2002

Use of molecular methods for genetic monitoring of an institutional mouse breeding colony.

It is important to perform genetic quality control on inbred mouse strains to minimize variability of genetic backgrounds. We used sensitive molecular methods to examine the genetic integrity of inbred mouse substrains maintained at an academic institution. Our goal, in part, was to compare the different molecular genetic monitoring methods to determine which were most sensitive, efficient, and beneficial in our genetic monitoring program. We examined the sensitivity and efficiency of simple sequence length polymorphism (SSLP) analysis of microsatellites and restriction fragment length polymorphism (RFLP) analysis of minisatellites with commercial, human, and synthetic mouse minisatellite probes. Although no polymorphisms were detected with the microsatellite analysis, certain minisatellite probes detected a small degree of polymorphism between our mouse substrains and the commercially available strains used as controls. Minisatellite probes also detected intra-substrain variation within our colonies; this variation probably represents mutations in highly unstable loci rather than genetic variation. Our analysis indicated that the genetic integrity of in-house C57BL/Ka, BALB/cKa, and C3H/Km inbred substrains had remained intact over 35 generations. Genetic monitoring by RFLP minisatellite analysis was more sensitive and efficient in detecting substrain differences than was SSLP microsatellite analysis. On the basis of these results, we established a strategy for future analysis of the in-house breeding colony.

Animal Husbandry↗
PubMed2005

Beyond pairwise distances: neighbor-joining with phylogenetic diversity estimates.

The "neighbor-joining algorithm" is a recursive procedure for reconstructing trees that is based on a transformation of pairwise distances between leaves. We present a generalization of the neighbor-joining transformation, which uses estimates of phylogenetic diversity rather than pairwise distances in the tree. This leads to an improved neighbor-joining algorithm whose total running time is still polynomial in the number of taxa. On simulated data, the method outperforms other distance-based methods. We have implemented neighbor-joining for subtree weights in a program called MJOIN which is freely available under the Gnu Public License at http://bio.math.berkeley.edu/mjoin/.

Algorithms↗
PubMedDate not supplied

Implementation of garlic cryopreservation techniques in the national plant germplasm system.

The USDA-ARS National Plant Germplasm System (NPGS) maintains more than 200 Allium sativum (garlic) accessions at the Western Regional Plant Introduction Station in Pullman, WA. All accessions must be grown out in the field annually since garlic plants from these accessions do not reliably produce seeds and bulbs do not store well. Shoot tips excised from garlic cloves can be successfully cryopreserved using either Plant Vitrification Solution 2 (PVS2; 15 percent v/v DMSO, 15 percent v/v ethylene glycol, 30 percent v/w glycerol, 0.4 M sucrose) or Plant Vitrification Solution 3 (PVS3; 50 percent v/w sucrose, 50 percent v/w glycerol). We compared regrowth of shoot tips representing diverse garlic germplasm after exposure to either PVS2 or PVS3 during the cryopreservation procedure. At the USDA-ARS National Center for Genetic Resources Preservation, a component of the NPGS, we consider accessions successfully preserved if a minimum of 40 percent of explants exhibit regrowth after liquid nitrogen exposure and at least 60 viable shoot tips remain in long-term storage. Ten of twelve diverse garlic accessions were successfully cryopreserved using either PVS2 or PVS3 as cryoprotectants. Five genotypes had the best post liquid nitrogen regrowth after exposure to PVS2, four genotypes had the best regrowth after exposure to PVS3, and three genotypes performed equally well using either cryoprotectant solution. This project is part of an ongoing program to cryopreserve accessions of NPGS clonal crop collections.

Cryopreservation↗
PubMed2003

Analysis of primate genomic variation reveals a repeat-driven expansion of the human genome.

We performed a detailed analysis of both single-nucleotide and large insertion/deletion events based on large-scale comparison of 10.6 Mb of genomic sequence from lemur, baboon, and chimpanzee to human. Using a human genomic reference, optimal global alignments were constructed from large (>50-kb) genomic sequence clones. These alignments were examined for the pattern, frequency, and nature of mutational events. Whereas rates of single-nucleotide substitution remain relatively constant (1-2 x 10(-9) substitutions/site/year), rates of retrotransposition vary radically among different primate lineages. These differences have lead to a 15%-20% expansion of human genome size over the last 50 million years of primate evolution, 90% of it due to new retroposon insertions. Orthologous comparisons with the chimpanzee suggest that the human genome continues to significantly expand due to shifts in retrotransposition activity. Assuming that the primate genome sequence we have sampled is representative, we estimate that human euchromatin has expanded 30 Mb and 550 Mb compared to the primate genomes of chimpanzee and lemur, respectively.

Animals↗