Biology subjects

Weir, B.

Publications and source records attributed to Weir, B..

7 recordsLinked to original sources

bioRxiv2024

Estimation of Jacquard's genetic identity coefficients with bi-allelic variants by constrained least-squares

The Jacquard genetic identity coefficients are of fundamental importance in relatedness research. We address the estimation of these coefficients as well as other relatedness parameters that derive from them such as kinship and inbreeding coefficients using a concise matrix framework. Estimation of the Jacquard coefficients via likelihood methods and the expectation-maximization algorithm is computationally very demanding for large numbers of polymorphisms. We propose a constrained least squares approach to estimate the Jacquard coefficients. A simulation study shows constrained least squares achieves root-mean-squared errors that are comparable with those of the maximum likelihood approach, in particular when founder allele frequencies are unknown, while obtaining enormous computational savings.

genetics↗

bioRxiv2023

Detecting inbreeding depression in structured populations

Measuring inbreeding as well as its consequences on fitness is central for many areas in biology including human genetics and the conservation of endangered species. However, there is no consensus on the most appropriate method, neither for quantification of inbreeding itself nor for the model to estimate its effect on specific traits. In this project, we simulated traits based on simulated genomes from a large pedigree and empirical whole-genome sequences of human data from populations with various sizes and structure (from the 1,000 Genomes project). We compare the ability of various inbreeding coefficients (F) to quantify the strength of inbreeding depression: allele sharing, two versions of the correlation of uniting gametes which differ in the weight they attribute to each locus and two identical-by-descent segments-based estimators. We also compare two models: the standard linear model and a linear mixed model including a genetic relatedness matrix (GRM) as random effect to account for the non-independence of observations. We find linear mixed models give better results in scenarios with population or family structure. Within the mixed models, we compare three different GRM matrices and show that in homogeneous populations, there is little difference among the different F and GRM for inbreeding depression quantification. However, as soon as strong population or family structure is present, the strength of inbreeding depression can be most efficiently estimated only if (i) the phenotypes are regressed on inbreeding coefficient based on a weighted version of the correlation of uniting gametes, which gives more weight to common alleles and (ii) with the GRM obtained from an allele sharing relatedness estimator.

genomics↗

bioRxiv2023

An allele-sharing, moment-based estimator of global, population specific and population pairs FST under a general model of population structure

Being able to properly quantify genetic differentiation is key to understanding the evolutionary potential of a species. One central parameter in this context is FST, the mean coancestry within populations relative to the mean coancestry between populations. Researchers have been estimating FST globally or between pairs of populations for a long time. More recently, it has been proposed to estimate population specific FST values, and between population-pair mean relative coancestry. Here, we review the several definitions and estimation methods of FST, and stress that they provide values relative to a reference population. We show the good statistical properties of an allele sharing, method of moments based estimator of FST (global, population specific and population pairs) under a very general model of population structure. We point to the limitation of existing likelihood and Bayesian estimators when the populations are not independent. Last, we show that recent attempts to estimate absolute, rather than relative, mean coancestry fail to do so. Author summary

evolutionary biology↗

bioRxiv2021

Population structure in the MHC region

In his 1972 "The apportionment of human diversity", Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection on specific genes and genomic regions can alter the apportionment of diversity. We examine genetic diversity at the HLA loci, located within the MHC region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The SNPs within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, with low FST values. However, when we analyze haplotypes defined by these SNPs (i.e., which define "HLA alleles"), we find marked differences in frequencies between geographic regions. These differences are not reflected in the FST values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting FST. Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We explore the case of Brazils bone-marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry.

genetics↗

bioRxiv2021

The transitivity of the Hardy-Weinberg law

The reduction of multi-allelic polymorphisms to variants with fewer alleles, two in the limit, is addressed. The Hardy-Weinberg law is shown to be transitive in the sense that a multi-allelic polymorphism that is in equilibrium will retain its equilibrium status if any allele together with its corresponding genotypes is deleted from the population. Similarly, the transitivity principle also applies if alleles are joined, which leads to the summation of allele frequencies and their corresponding genotype frequencies. These basic polymorphism properties are intuitive, but they have apparently not been formalized or investigated. This article provides a straightforward proof of the transitivity principle, and its usefulness in practical genetic data analysis with multi-allelic markers is explored. In general, results of statistical tests for Hardy-Weinberg equilibrium obtained with polymorphisms that are reduced by deletion or joining of alleles are seen to be consistent with the formulated transitivity principle. We also show how the transitivity principle allows one to identify equilibrium-offending alleles, and how it can provide clues to genotyping problems and evolutionary changes. For microsatellites, which are widely used in forensics, the transitivity principle implies one expects similar results for statistical tests that use length-based and sequence-based alleles. High-quality autosomal microsatellite databases of the US National Institute of Standards and Technology are used to illustrate the use of the transitivity principle in testing both length-based and sequence-based microsatellites for Hardy-Weinberg proportions. Test results for Hardy-Weinberg proportions for the two types of microsatellites are seen to be largely consistent and can detect allele imbalance.

genetics↗

bioRxiv2020

Genome-wide identification and transcriptional analyses of MATE transporter genes in root tips of wild Cicer spp. under aluminium stress

Chickpea is an economically important legume crop with high nutritional value in human diets. Aluminium-toxicity poses a significant challenge for the yield improvement of this increasingly popular crop in acidic soils. The wild progenitors of chickpea may provide a more diverse gene pool for Al-tolerance in chickpea breeding. However, the genetic basis of Al-tolerance in chickpea and its wild relatives remains largely unknown. Here, we assessed the Al-tolerance of six selected wild Cicer accessions by measuring the root elongation in solution culture under control (0 {micro}M Al3+) and Al-treatment (30 {micro}M Al3+) conditions. Al-treatment significantly reduced the root elongation in all target lines compared to the control condition after 2-days growth. However, the relative reduction of root elongation in different lines varied greatly: 3 lines still retained significant root growth under Al-treatment, whilst another 2 lines displayed no root growth at all. We performed genome-wide identification of multidrug and toxic compound extrusion (MATE) encoding genes in the Cicer genome. A total of 56 annotated MATE genes were identified, which divided into 4 major phylogeny groups (G1-4). Four homologues to lupin LaMATE (> 50% aa identity; named CaMATE1-4) were clustered with previously characterised MATEs related to Al-tolerance in various other plants. qRT-PCR showed that CaMATE2 transcription in root tips was significantly up-regulated upon Al-treatment in all target lines, whilst CaMATE1 was up-regulated in all lines except Bari2_074 and Deste_064, which coincided with the lines displaying no root growth under Al-treatment. Transcriptional profiling in five Cicer tissues revealed that CaMATE1 is specifically transcribed in the root tissue, further supporting its role in Al-detoxification in roots. This first identification of MATE-encoding genes associated with Al-tolerance in Cicer paves the ways for future functional characterization of MATE genes in Cicer spp., and to facilitate future design of gene-specific markers for Al-tolerant line selection in chickpea breeding programs.

plant biology↗

bioRxiv2017

Multi-allelic Exact tests for Hardy-Weinberg equilibrium that account for gender

Statistical tests for Hardy-Weinberg equilibrium are important elementary tools in genetic data analysis. X-chromosomal variants have long been tested by applying autosomal test procedures to females only, and gender is usually not considered when testing autosomal variants for equilibrium. Recently, we proposed specific X-chromosomal exact test procedures for bi-allelic variants that include the hemizygous males, as well as autosomal tests that consider gender. In this paper we present the extension of the previous work for variants with multiple alleles. A full enumeration algorithm is used for the exact calculations of tri-allelic variants. For variants with many alternate alleles we use a permutation test. Some empirical examples with data from the 1000 genomes project are discussed.

genetics↗