Pedigree Approach Research Articles

On pedigree polytope and its properties

The fact that linear optimization over a polytope can be done in polynomial time in the input size of the instance, has created renewed interest in studying 0-1 polytopes corresponding to combinatorial optimization problems. Studying their polyhedral structure has resulted in new algorithms to solve very large instances of some difficult problems like the symmetric traveling salesman problem. The multistage insertion formulation ( MI ) given by the author, in 1982, for the symmetric traveling salesman problem (STSP), gives rise to a combinatorial object called the pedigree. The pedigrees are in one-to-one correspondence with Hamiltonian cycles. Given n , the convex hull of all the pedigrees is called the corresponding pedigree polytope. In this article we bring together the research done a little over a decade by the author and his doctoral students, on the pedigree polytope, its structure, membership problem and properties of the MI formulation for the STSP. In addition we summarise some of the computational and other peripheral results relating to pedigree approach to solve the STSP. The pedigree polytope possesses properties not shared by the STSP (tour) polytope, which makes it interesting to study the pedigrees, both from theoretical and algorithmic perspectives.

Genetic parameter estimates for growth-related traits of blunt snout bream (Megalobrama amblycephala) using microsatellite-based pedigree

Blunt snout bream (Megalobrama amblycephala) is an herbivorous freshwater fish species native to China and has been recognized as a main aquaculture species in the Chinese freshwater polyculture system with high economic value. The genetic parameter estimates for important economic traits are needed for its selective breeding. The aim of this study was to estimate the heritabilities for its growth-related traits and explore the genetic and phenotypic correlations among the traits using microsatellite-based pedigree approach. Offspring from a mass-spawning of 92 broodstocks (42 sires and 50 dams) were reared in a communal pond and nine microsatellites were used to identify the parents of each sampled offspring. Of 749 offspring randomly selected, 708 (94.53%) could be assigned directly to a single parental pair, which was used for heritability estimates. Data were analysed using the method of restricted maximum likelihood (REML) using animal model and the results showed that the heritabilities of body weight, body length, total length and body height were 0.65, 0.53, 0.53 and 0.50, respectively. High genetic correlations were found among these four traits. According to these results, selection for growth seems to be feasible in M. amblycephala and the other growth traits will be heightened accordingly with the selection based on body length.

Genetic diversity, inbreeding and breeding practices in dogs: Results from pedigree analyses

Pedigree analysis constitutes a classical approach for the study of the evolution of genetic diversity, genetic structure, history and breeding practices within a given breed. As a consequence of selection pressure, management in closed populations and historical bottlenecks, many dog breeds have experienced considerable inbreeding and show (on the basis of a pedigree approach) comparable diversity loss compared to other domestic species. This evolution is linked to breeding practices such as the overuse of popular sires or mating between related animals. The popular sire phenomenon is the most problematic breeding practice, since it has also led to the dissemination of a large number of inherited defects. The practice should be limited by taking measures such as restricting the number of litters (or offspring) per breeding animal.

Genetic Transmission of Cytochrome P450 2D6 (CYP2D6) Ultrarapid Metabolism: Implications for Breastfeeding Women taking Codeine

The pro-drug codeine is commonly prescribed for postpartum pain relief in North America. The safety of codeine during breastfeeding is related in part to the extent of the active morphine metabolite catalyzed from codeine via the cytochrome P450 2D6 (CYP2D6) enzyme. In mothers who have greater than two functional copies of the CYP2D6 gene (CYP2D6 ultrarapid metabolism phenotype; UM) a substantially higher proportion of morphine is produced. Label changes on codeine-containing medications will highlight the risks associated with this genotype for breastfeeding mothers, but are not supported by translation strategies on how to incorporate this pharmacogenetic knowledge into clinical practice. To address the immediate issue of CYP2D6 UM inheritance in family members of a breastfed infant who succumbed to fatal opioid intoxication and whose codeine-prescribed mother was a CYP2D6 UM, we constructed a pedigree. While the pedigree approach is helpful to aid diagnosis, identify other at risk family members, and simplify pharmacogenetic analysis, its clinical usefulness is dependant on an institutional framework which is not available in most centers at this time.

Data uncertainty assessment and information flow analysis for product-service systems in a library case study

The provision of service is increasingly becoming a key driver for delivering customer value. This emphasis on service provision is promoted by approaches such as Product-Service Systems (PSSs) that deliver value in use based on integrated products and services. However, to achieve effective delivery of services, it is important to manage information flow and data uncertainty associated with information requirement. The paper proposes a methodology that consists of: (a) the assessment of data uncertainty through the numeral, unit, spread, assessment and pedigree approach and a pedigree matrix consisting of data uncertainties to be scored based on their influence on the system; and (b) the analysis of information flow by means of data flow diagrams that depict information exchanges and an info-dynamic engine that measures the efficiency and recommends improvements for information flows in PSSs. A library case study was undertaken to show how such a methodology can be applied.

Families in space: relatedness in the Barents Sea population of polar bears (Ursus maritimus)

The kin structure and dispersal pattern of polar bears (Ursus maritimus) of the Barents Sea was investigated during the spring mating season using two complementary approaches. First, individual genotypes based on the analyses of 27 microsatellite loci of 583 polar bears were related to field information gathered from 1146 bears in order to reconstruct the animals' pedigrees and to infer geographical distances between adult bears of different relatedness categories. According to the data, the median natal dispersal distance of the male animals was 52 km while that of the females was 93 km. Second, the relatedness of pairs of adult bears was estimated and correlated to the geographical distance between them. The female dyads had a much stronger kin structure than the male dyads. The 'pedigree approach' revealed a male kin structure which could not be detected using the 'relatedness approach'. This suggests that, on a broader scale, effective dispersal is slightly male biased. Despite fidelity to natal areas, male-mediated gene flow may nevertheless prevent genetic differentiation. Males might occasionally shift their home range which could therefore lead to a male-biased breeding dispersal. Our results showed that a nonterritorial species such as the polar bear that has a high dispersal potential, lives in a highly unstable environment and migrates seasonally is still able to exhibit a distinct kin structure during the mating season.

Wild pedigrees: the way forward

Metrics derived from pedigrees are key to investigating several major issues in evolutionary biology, including the quantitative genetic architecture of traits, inbreeding depression, and the evolution of cooperation and inbreeding avoidance. There is merit in studying these issues in natural populations experiencing spatially and temporally variable environmental conditions, since these analyses may yield different results from laboratory studies and allow us to understand population responses to rapid environmental change. Partial pedigrees are now available for several natural populations which are the subject of long-term individual-based studies, and analyses using these pedigrees are leading to important insights. Accurate pedigree construction supported by molecular genetic data is now feasible across a wide range of taxa, and even where only imprecise pedigrees are available it is possible to estimate the consequences of imprecision for the questions of interest. In outbred diploid populations, the pedigree approach is superior to analyses based on marker-based pairwise estimators of coancestry.

Enhancing Salt Tolerance in Crops Through Molecular Breeding: A New Strategy

SUMMARY Salinity limits crop production in many rainfed ecosystems and is an increasing problem in irrigated areas. Developing and developed countries alike need more efficient methods of enhancing salt tolerance in crops. The traditional breeding approach consists of (i) screening germplasm collections for donors of salt tolerance, (ii) crossing a donor with an elite line and advancing the F1 hybrid to about the F7 or F8 generation while selecting for elite traits, and concurrently (iii) selecting for salt tolerance starting at about the F4 generation. The low efficiency of this pedigree approach is due principally to the difficulty of recovering elite genotypes with salt tolerance traits, the genetic complexity of salt tolerance, and the strength of genotype × environment interactions (GEI). Advances in genomics are making possible an alternative approach in which a pre-breeding phase is used to pyramid several known genes and finely mapped major QTLs for complementary aspects of salt tolerance. The known genes can include transgenes modified by deliberate mutation or promoter switching. DNA-based selection protocols that are used to pyramid these genes are again employed during the breeding phase to transfer the entire set of genes for salt tolerance into any elite line by backcrossing. Breeding efficiency is increased because (i) elite traits are more easily recovered by backcrossing than by the pedigree approach, (ii) the genetic complexity of salt tolerance is reduced to a small set of well-defined genes and loci of large effect, (iii) the confounding effects of GEI are eliminated from the breeding phase, and (iv) the investment in gene discovery and QTL mapping can be recouped by transferring the same set of genes to a range of recipient lines that require salt tolerance. Efficiency will increase over time as more genes are added to the gene set and as QTL are replaced by the corresponding gene. Here we summarize the scientific advances underlying this new strategy, which should be applicable to other complex traits such as drought tolerance, durable resistance to pests and diseases, yield potential and product quality.

Effective population size, reproductive success and sperm precedence in the butterfly, Bicyclus anynana, in captivity.

A pedigree approach is used to estimate the effective population size yn two population cages of the butterfly, Bicyclus anynana. Each cage was founded with 54 individually marked adults of each sex. Matings were recorded over a 3-day period. Eggs were then collected from each female over a similar period before the numbers of hatching larvae were counted to assess progeny number. The males showed a higher variance in reproductive success than the females. Since about one-quarter of all females mated more than once, we also examined the pattern of sperm precedence using molecular markers or, in separate crossing experiments, wing pattern mutants. Both instances of complete first and last male sperm precedence, as well as of sperm mixing, were found. In some crosses a 'leakiness' was found in which some of the early eggs laid by a female were fertilized by a male partner which was subsequently completely unsuccessful. However, the estimates of effective population size were largely unaffected by the pattern of sperm precedence. Estimates for Ne : N in each cage were close to 0.60. The possibility of obtaining comparable estimates in selected natural populations of butterflies is discussed.

Genetic approaches to understanding the pathophysiology of complex human traits

Genetic approaches to understanding the pathophysiology of complex human traits, for example, hypertension, can complement physiologic analyses and are likely to improve our ability to treat or prevent the disease. A particularly useful approach is to perform linkage analysis with candidate genes using intermediate phenotypes. This has proven successful so far in identifying two genes involved in hypertension. The first was a fusion gene mutation which linked the regulatory region of the 11B-hydroxylase gene to the coding sequence for the protein of aldosterone synthetase. This mutant gene is responsible for the condition glucocorticoid-remediable aldosteronism (GRA). The intermediate phenotype used was increased levels of the adrenal steroids 18-oxo and hydroxycortisol. The gene for GRA was identified using a pedigree approach. It is likely, to identify other genes in hypertension, that the most appropriate population to be affected would be sib pairs, that is, sibling pairs who both have hypertension. In a recent study the angiotensinogen gene also was linked to hypertension in individuals who had severe or early onset hypertension. In addition, a variant of the angiotensinogen gene, substitution of threonine rather than methionine at codon 235, was specifically associated with hypertension. In a separate study, the T235 homozygote of the angiotensinogen gene was associated with the non-modulating intermediate phenotype of essential hypertension. Since converting enzyme inhibitors appear to correct the specific defect underlying the elevated blood pressure in non-modulators, identification of the gene potentially associated with non-modulation raises the strong possibility that genetic screening will allow for more specific therapy.

Continuity and change in infant shyness from 14 to 20 months

Objective measures of shyness in the MacArthur Longitudinal Twin Study were obtained in two testing situations: the laboratory and the home. A longitudinal hierarchical model was fitted to the data, allowing estimation of the extent to which genetic, shared environmental, and unique environmental influences contributed to continuity and change of the shyness phenotype from 14 to 20 months of age. The sample consisted of 163 monozygotic and 138 same-sex dizygotic twin pairs. Models were fitted to raw data using a maximum-likelihood pedigree approach. Genetic, shared environmental, and unique environmental first-order factors, with specific variances, were modeled on each of four shyness ratings assessed in the laboratory and home at 14 and 20 months. Four second-order genetic, shared environmental, and unique environmental factors were also modeled. Results indicated that developmental change from 14 to 20 months and situational specificity between the laboratory and the home are mediated largely by shared and unique environmental influences. Genetic variation is largely responsible for both the stability in shyness from 14 to 20 months and the phenotypic correlations observed between the laboratory and the home settings.