Genetic Differentiation of Clariid Populations using Microsatellite Markers in Kano State Rivers

This study aimed to investigate the genetic characterization of strains of Clariid fish species in some river bodies in Kano State using microsatellite markers.One hundred and seventy seven Clariid fish samples (Clariasgariepinus and Heterobranchuslongifilis) were collected from six rivers (Thomas, Ghari, Tiga dam, Duddurun Gaya, Karaye and Bagwai) in Kano state. Blood sample was taken from each fish sample by severing the caudal peduncle and drained into FTA cards for DNA extraction, Polymerase Chain Reaction and electrophoresis to determine genetic variation between the Clariid fish populations.Genealex 6.4 software package was used to analyse the resolve bands from DNA extraction to determine their base pair and genetic variation. Results showed that the Fst values ranged from 0.00 to 0.66, Fit ranged from -0.04 to 0.12, Fis ranged from -0.35 to -0.26. It indicated a large number of gene flow (exchange) among the populations with a range of 0.46 to 0.87. There was an established magnitude of genetic divergence (91.86%) among the populations as shown by the result of the percentage polymorphism which depends on the number of alleles detected per locus and their frequencies. It can be concluded that since there was no inbreeding as shown in the study, none of the population exhibited genetic uniqueness. The populations had a high genetic differentiation between populations but moderate differentiation within populations. The populations were outbred populations; an indication that relatives avoided mating in the population.

Long runs of homozygosity are associated with Alzheimer’s disease

Long runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD); however, their search has been poorly assessed to date. To investigate homozygosity in AD, here we performed a fine-scale ROH analysis using 10 independent cohorts of European ancestry (11,919 AD cases and 9181 controls.) We detected an increase of homozygosity in AD cases compared to controls [βAVROH (CI 95%) = 0.070 (0.037–0.104); P = 3.91 × 10−5; βFROH (CI95%) = 0.043 (0.009–0.076); P = 0.013]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 × 10−16). A significant ROH association with AD risk was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), (β (CI 95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 × 10−4), previously related to AD. Next, to search for recessive candidate variants in ROHs, we constructed a homozygosity map of inbred AD cases extracted from an outbred population and explored ROH regions in whole-exome sequencing data (N = 1449). We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability.

Discovery of runs-of-homozygosity diplotype clusters and their associations with diseases in UK Biobank

Runs of homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE, to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number of individuals, in large cohorts. ROH-DICE identified over 1 million ROH diplotypes that span over 100 SNPs and shared by more than 100 UK Biobank participants. Moreover, we found significant associations of clustered ROH diplotypes across the genome with various self-reported diseases, with the strongest associations found between the extended HLA region and autoimmune disorders. We found an association between a diplotype covering the HFE gene and haemochromatosis, even though the well-known causal SNP was not directly genotyped nor imputed. Using genome-wide scan, we identified a putative association between carriers of an ROH diplotype in chromosome 4 and an increase of mortality among COVID-19 patients. In summary, our ROH-DICE method, by calling out large ROH diplotypes in a large outbred population, enables further population genetics into the demographic history of large populations. More importantly, our method enables a new genome-wide mapping approach for finding disease-causing loci with multi-marker recessive effects at population scale.

Genomically Aided Diagnosis of Severe Developmental Disorders

Our ability to make accurate and specific genetic diagnoses in individuals with severe developmental disorders has been transformed by data derived from genomic sequencing technologies. These data reveal both the patterns and rates of different mutational mechanisms and identify regions of the human genome with fewer mutations than would be expected. In outbred populations, the most common identifiable cause of severe developmental disorders is de novo mutation affecting the coding region in one of approximately 500 different genes, almost universally showing constraint. Simply combining the location of a de novo genomic event with its predicted consequence on the gene product gives significant diagnostic power. Our knowledge of the diversity of phenotypic consequences associated with comparable diagnostic genotypes at each locus is improving. Computationally useful phenotype data will improve diagnostic interpretation of ultrarare genetic variants and, in the long run, indicate which specific embryonic processes have been perturbed.

Creating outbred and inbred populations of haplodiploid mites to measure adaptive responses in the lab

Laboratory studies are often criticized for not being representative of processes occurring in natural populations. This can be partially mitigated by using lab populations that capture large amounts of variation. Additionally, many studies addressing adaptation of organisms to their environment are done with laboratory populations, using quantitative genetics or experimental evolution methodologies. Such studies rely on populations that are either highly outbred or inbred. However, the methodology underlying the generation of such biological resources are usually not explicitly documented.Given their small size, short generation time, amenability to laboratory experimentation and knowledge of their ecological interactions, haplodiploid spider mites are becoming a widely used model organism. Here, we describe the creation of outbred populations of two species of spider mites, Tetranychus urticae and T. evansi, obtained by performing controlled crosses between individuals from field-collected populations. Subsequently, from the outbred population of T. evansi, we derived inbred lines, by performing several generations of sib-mating. These can be used to measure broad-sense heritability as well as correlations among traits. Finally, we outline an experimental evolution protocol that can be widely used in other systems. Sharing these biological resources with other laboratories and combining them with the available powerful genetic tools for T. urticae (and other species) will allow consistent and comparable studies that greatly contribute to our understanding of ecological and evolutionary processes.

Autosomal Recessive Alzheimer’s disease (arAD): homozygosity mapping of genomic regions containing arAD loci

ABSTRACTLong runs of homozygosity (ROH) are contiguous stretches of homozygous genotypes, which are a footprint of recent inbreeding and recessive inheritance. The presence of recessive loci is suggested for Alzheimer’s disease (AD). However, the search for recessive variants has been poorly assessed to date. To investigate homozygosity in AD, we performed a fine-scale ROH analysis including 21,100 individuals from 10 cohorts of European ancestry (11,919 AD cases and 9,181 controls). We detected an increase of homozygosity in AD cases compared to controls [βFROH (CI95%) = 0.051 (0.023 – 0.078); P = 3.25 x 10-4]. ROHs increasing the risk of AD (OR > 1) were significantly overrepresented compared to ROHs increasing protection (p < 2.20 x 10-16). The top associated ROH with AD risk (β (CI95%) = 1.09 (0.48 ‒ 1.48), p value = 9.03 x 10-4) was detected upstream the HS3ST1 locus (chr4:11,189,482‒11,305,456), previously related to AD. Next, to construct a homozygosity map of AD cases, we selected ROHs shared by inbred AD cases extracted from an outbred population. We used whole-exome sequencing data from 1,449 individuals from the Knight-ADRC-NIA-LOAD (KANL) cohort to identify potential recessive variants in candidate ROHs. We detected a candidate marker, rs117458494, mapped in the SPON1 locus, which has been previously associated with amyloid metabolism. Here, we provide a research framework to look for recessive variants in AD using outbred populations. Our results showed that AD cases have enriched homozygosity, suggesting that recessive effects may explain a proportion of AD heritability.

Affective Pavlovian motivation is enhanced in obesity susceptible populations; implications for incentive motivation in obesity

Global obesity rates continue to rise, presenting a major challenge to human health. Efforts to uncover the drivers of this epidemic have highlighted the contribution of Pavlovian motivational processes to overeating. In humans, brain and behavioral reactivity to food related stimuli positively correlates with subsequent weight gain. In concordance with this, selectively bred obesity-prone rats exhibit stronger cue-triggered food-seeking via single outcome Pavlovian-to-instrumental transfer (SO PIT) than obesity-resistant rats. These data show that Pavlovian motivation is stronger in selectively bred obesity-prone groups. However, whether obesity susceptibility in outbred populations is associated with enhanced PIT is unknown. Moreover, PIT can arise via two neurobehaviorally dissociable processes, a sensory specific versus a general affective process that cannot be distinguished by SO PIT. Thus, it is unclear which PIT process is enhanced in obesity-prone groups. Therefore, we determined whether obesity susceptibility in outbred populations is associated with enhanced Sensory Specific (SS) PIT or General PIT and whether expression of these forms of PIT differs between selectively bred obesity-prone versus obesity-resistant rats. We find that in outbred rats, the magnitude of General PIT is positively correlated with subsequently determined obesity susceptibility. In selectively bred rats, the magnitude of General PIT was stronger in obesity-prone versus obesity-resistant groups. Jointly, these data show that enhanced affective Pavlovian motivation is tightly linked to obesity vulnerability, supporting a role for phenotypic differences in incentive motivation for the development of obesity. This has important implications for obesity prevention and for understanding the neurocircuitry mediating enhanced food-seeking in vulnerable individuals.

A clinal polymorphism in the insulin signaling transcription factorfoxocontributes to life-history adaptation inDrosophila

A fundamental aim of adaptation genomics is to identify polymorphisms that underpin variation in fitness traits. InD. melanogasterlatitudinal life-history clines exist on multiple continents and make an excellent system for dissecting the genetics of adaptation. We have previously identified numerous clinal SNPs in insulin/insulin-like growth factor signaling (IIS), a pathway known from mutant studies to affect life history. However, the effects of natural variants in this pathway remain poorly understood. Here we investigate how two clinal alternative alleles atfoxo, a transcriptional effector of IIS, affect fitness components (viability, size, starvation resistance, fat content). We assessed this polymorphism from the North American cline by reconstituting outbred populations, fixed for either the low- or high-latitude allele, from inbred DGRP lines. Since diet and temperature modulate IIS, we phenotyped alleles across two temperatures (18°C, 25°C) and two diets differing in sugar source and content. Consistent with clinal expectations, the high-latitude allele conferred larger body size and reduced wing loading. Alleles also differed in starvation resistance and expression ofInR, a transcriptional target of FOXO. Allelic reaction norms were mostly parallel, with few GxE interactions. Together, our results suggest that variation in IIS makes a major contribution to clinal life-history adaptation.