Major Gene Effect Research Articles

Quantum Capacitance Based Amplified Graphene Phononics for Studying Neurodegenerative Diseases.

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease (MND) characterized by a rapid loss of upper and lower motor neurons resulting in patient death from respiratory failure within 3-5 years of initial symptom onset. Although at least 30 genes of major effect have been reported, the pathobiology of ALS is not well understood. Compounding this is the lack of a reliable laboratory test which can accurately diagnose this rapidly deteriorating disease. Herein, we report on the phonon vibration energies of graphene as a sensitive measure of the composite dipole moment of theinterfaced cerebrospinal fluid (CSF) that includes a signature-compositionspecific to the patients with ALS disease. The second-order overtone of in-plane phonon vibration energy (2D peak) of graphene shifts by 3.2 ± 0.5 cm-1 for all ALS patients studied in this work. Further, the amount of n-doping-induced shift in the phonon energy of graphene, interfaced with CSF, is specific to the investigated neurodegenerative disease (ALS, multiple sclerosis, and MND). By removing a severe roadblock in disease detection, this technology can be applied to study diagnostic biomarkers for researchers developing therapeutics and clinicians initiating treatments for neurodegenerative diseases.

Genotype frequency of FecXB (Belclare) mutation of BMP15 gene in Chios (Sakiz) sheep

Ovulation rate and litter size, varies between breeds or individulas who belong to the same breed, are evaluated as fertility traits. Fertility traits are important for economic values in animal breeding. However these traits exhibit only in females and they are determined in the later stages of lifes. Hence the genetic perspective is more effective way to confirm the fertility capacities early period of life time. Fecundity genes such as BMP15 regulate the fertility traits by increasing the ovulation rate due to the occuring mutations. Despite some prolific breed were investigated for FecXB mutation; the researches carried out to determine thatmutation in Chios sheep breed are limited. The objective of the current study was to estimate the the genotype frequencies of FecXB mutation of BMP15 gene in prolific Chios sheep. We investigated the FecXB mutation by PCR-RFLP method in Chios sheep (n=77). According to result, the investigated Chios breed was found monomorphic for FecXB mutation. All individuals were digested by DdeI restriction enzyme and showed wild-type genotype and did not carry FecXB mutation nin present study. In conclusion it’s thought that the high prolificacy in Chios sheep may be based on another region of BMP15 gene or different major gene. Thus the effect of other major genes or regions/QTL’s should be investigated in future studies with a large number of animals.

Segregation analyses of 123 families: dominant genes commonly contribute to pathogenesis of endometriosis

At the 2018 Society for Reproductive Investigation meeting, we described the largest endometriosis family reported to date: spanning 19 generations with 218 women with surgically confirmed disease. An autosomal major gene effect is likely in this family. In this study, we examined the risk of endometriosis in 123 smaller families with probands selected from the same time period and unrelated to the index pedigree. Genetic segregation analysis. 123 probands are surgically affected women with a birth date between 1960 and 1995 (this date range chosen to focus on adult women with the highest likelihood of a surgical diagnosis). These probands have no known ancestral relationship to the large index pedigree by genealogy records or DNA ancestry methods. Three-generation family histories were collected and any reported endometriosis was confirmed with surgical records. Segregation analyses were performed. Prevalence of endometriosis in close relatives is much higher than the 2-3% prevalence of surgically diagnosed endometriosis in the general population. The rates observed are also much higher than expected with multifactorial polygenic inheritance.Tabled 1Index Endometriosis Pedigree: descendants of common ancestor born in 1608Present Study: Matched Recent ProbandsNumber%Number%Confirmed affected and born between 1960-199589123Sisters affected /total58/17433%62/36717%Mothers affected /total9/8910%29 /12324%First cousins affected /total21/8226%30/13023%Adult daughters affected /total3/1225%1/812% Open table in a new tab . Analysis of larger number of families confirms that autosomal dominant, high penetrance risk alleles for endometriosis segregate in some families. The heritability of endometriosis may be higher than estimated by older twin studies.

Genetic Susceptibility to Leprosy—From Classic Immune-Related Candidate Genes to Hypothesis-Free, Whole Genome Approaches

Genetics plays a crucial role in controlling susceptibility to infectious diseases by modulating the interplay between humans and pathogens. This is particularly evident in leprosy, since the etiological agent, Mycobacterium leprae, displays semiclonal characteristics not compatible with the wide spectrum of disease phenotypes. Over the past decades, genetic studies have unraveled several gene variants as risk factors for leprosy per se, disease clinical forms and the occurrence of leprosy reactions. As expected, several of these genes are immune-related; yet, hypothesis-free approaches have led to genes not classically linked to immune response. The PARK2, originally described as a Parkinson’s disease gene, illustrates the case: Parkin—the protein coded by PARK2—was defined as an important player regulating innate and adaptive immune responses only years after its description as a leprosy susceptibility gene. Interestingly, even with the use of powerful hypothesis-free study designs such as genome-wide association studies, most of the major gene effect controlling leprosy susceptibility remains elusive. One hypothesis to explain this “hidden heritability” is that rare variants not captured by classic association studies are of critical importance. To address this question, massively parallel sequencing of large segments of the human genome—even whole exomes/genomes—is an alternative to properly identify rare, disease-causing mutations. These mutations may then be investigated through sophisticated approaches such as cell reprogramming and genome editing applied to create in vitro models for functional leprosy studies.

Utility of pooled sequencing for association mapping in nonmodel organisms.

High-density genome-wide sequencing increases the likelihood of discovering genes of major effect and genomic structural variation in organisms. While there is an increasing availability of reference genomes across broad taxa, the greatest limitation to whole-genome sequencing of multiple individuals continues to be the costs associated with sequencing. To alleviate excessive costs, pooling multiple individuals with similar phenotypes and sequencing the homogenized DNA (Pool-Seq) can achieve high genome coverage, but at the loss of individual genotypes. Although Pool-Seq has been an effective method for association mapping in model organisms, it has not been frequently utilized in natural populations. To extend bioinformatic tools for rapid implementation of Pool-Seq data in nonmodel organisms, we developed a pipeline called PoolParty and illustrate its effectiveness in genetic association mapping. Alignment expectations based on five pooled Chinook salmon (Oncorhynchus tshawytscha) libraries showed that approximately 48% genome coverage per library could be achieved with reasonable sequencing effort. We additionally examined male and female O.tshawytscha libraries to illustrate how Pool-Seq techniques can successfully map known genes associated with functional differences among sexes such as growth hormone 2. Finally, we compared pools of individuals of different spawning ages for each sex to discover novel genes involved with age at maturity in O.tshawytscha such as opsin4 and transmembrane protein19. While not appropriate for every system, Pool-Seq data processed by the PoolParty pipeline is a practical method for identifying genes of major effect in nonmodel organisms when high genome coverage is necessary and cost is a limiting factor.

Genetic Architecture and Candidate Genes for Deep-Sowing Tolerance in Rice Revealed by Non-syn GWAS.

Dry direct-seeding of rice is rapidly increasing in China, but variable planting depth associated with machine sowing can lead to low seedling emergence rates. Phenotype analysis of 621 rice accessions showed that mesocotyl length (ML) was induced by deep soil covering and was important in deep-sowing tolerance in the field. Here, we performed and compared GWAS using three types of SNPs (non-synonymous SNP, non-synonymous SNPs and SNPs within promoters and 3 million randomly selected SNPs from the entire set of SNPs) and found that Non-Syn GWAS (GWAS using non-synonyomous SNP) decreased computation time and eliminated confounding by other loci relative to GWAS using randomly selected SNPs. Thirteen QTLs were finally detected, and two new major-effect genes, named OsML1 and OsML2, were identified by an integrated analysis. There were 2 and 7 non-synonymous SNPs in OsML1 and OsML2, respectively, from which 3 and 4 haplotypes were detected in cultivated rice. Combinations of superior haplotypes of OsML1 and OsML2 increased ML by up to 4 cm, representing high emergence rate (85%) in the field with 10 cm of soil cover. The studies provide key loci and naturally occurring alleles of ML that can be used in improving tolerance to dry direct-seeding.

A Spontaneous Mutation in Taar1 Impacts Methamphetamine-Related Traits Exclusively in DBA/2 Mice from a Single Vendor

Major gene effects on traits associated with substance use disorders are rare. Previous findings in methamphetamine drinking (MADR) lines of mice, bred for high or low voluntary MA intake, and in null mutants demonstrate a major impact of the trace amine-associated receptor 1 (Taar1) gene on a triad of MA-related traits: MA consumption, MA-induced conditioned taste aversion and MA-induced hypothermia. While inbred strains are fundamentally genetically stable, rare spontaneous mutations can become fixed and result in new or aberrant phenotypes. A single nucleotide polymorphism in Taar1 that encodes a missense proline to threonine mutation in the second transmembrane domain (Taar1m1J) has been identified in the DBA/2J strain. MA is an agonist at this receptor, but the receptor produced by Taar1m1J does not respond to MA or endogenous ligands. In the present study, we used progeny of the C57BL/6J × DBA/2J F2 cross, the MADR lines, C57BL/6J × DBA/2J recombinant inbred strains, and DBA/2 mice sourced from four vendors to further examine Taar1-MA phenotype relations and to define the chronology of the fixation of the Taar1m1J mutation. Mice homozygous for Taar1m1J were found at high frequency early in selection for high MA intake in multiple replicates of the high MADR line, whereas Taar1m1J homozygotes were absent in the low MADR line. The homozygous Taar1m1J genotype is causally linked to increased MA intake, reduced MA-induced conditioned taste aversion, and reduced MA-induced hypothermia across models. Genotype-phenotype correlations range from 0.68 to 0.96. This Taar1 polymorphism exists in DBA/2J mice sourced directly from The Jackson Laboratory, but not DBA/2 mice sourced from Charles River (DBA/2NCrl), Envigo (formerly Harlan Sprague Dawley; DBA/2NHsd) or Taconic (DBA/2NTac). By genotyping archived samples from The Jackson Laboratory, we have determined that this mutation arose in 2001–2003. Our data strengthen the conclusion that the mutant Taar1m1J allele, which codes for a non-functional receptor protein, increases risk for multiple MA-related traits, including MA intake, in homozygous Taar1m1J individuals.

A genomic investigation on hybrid sterility in house mouse using a two stage model

Genome wide association studies (GWASs) commonly used to search for genetic variants associated with quantitative traits. Pleiotropic effect of genes may cause the observed correlations among different phenotypes. This study proposed a two stage multilocus model for pleiotropic GWAS using a Bayesian mixture model to take into account of both small and major gene effects. The objectives of this study were to investigate if the two-stage model was useful for detecting pleiotropic genes using a simulated data set and to investigate existence of pleiotropic genes for testis weight and testis gene expression levels in house mouse. The analyses included relative testis weight and testis gene expression traits. The results showed that two stage model had higher power to detect the pleiotropic QTL than the single marker model. It was also noted the possible economical impact of sampling informative individuals for the GWAS analyses by observing genomic trends in the simulated dataset. Two stage model detected 50 and 53 major SNP effects using first and the second principal components. Additive genetic variation explained by chromosome X was found to be 4% for the testis weight.

Evaluation of Advanced Bread Wheat Lines for Field and Seedling Resistance to Stem Rust (<i>Puccinia graminis</i> f. sp. <i>tritici</i>)

Field-based adult plant resistance assessment at multi-location rust hot spot sites is a crucial job for those plant pathologists screening several wheat lines at a time against the rusts. Rust resistant bread wheat genotypes that have been extracted from previous studies have sustained wheat production in Ethiopia. The objective of this study was to evaluate advanced bread wheat lines extracted from wheat breeding trials against stem rust at adult plat stage under stem rust hot spot sites and at seedling stages in the greenhouse. Eighty three lines were further re-evaluated in consecutive two years. Check varieties were included for comparison. High disease pressure was developed on adult plant in the trial as it has been revealed by high severity on susceptible check varieties. Over years average final rust severity, co-efficient of infection and field reaction have used for differentiating Adult plant resistances. Based on ACI, the 843 genotypes evaluated in initial trial in 2013 were categorized into 10 resistance levels, of which 188 genotypes were in high level resistance category, revealing that various level of adult plant resistance is operating in these test materials. Most of 83 genotypes r-evaluated in consecutive two years after initial stage have sustained low final stem rust severity and coefficient of infection as compared with check varieties. Genotypes were varied by adult plant reaction to stem rust, however, lines ETBW7818, ETBW7819, ETBW7258, ETBW 8008, ETBW 8009, ETBW 8017, ETBW 8027, ETBW 8052, ETBW 8054 and ETBW 8055 concisely showed a reaction of R to R-MR invariably with environments. Of the 83 lines tested at seedling stages against four races, 21 lines exhibited resistance to three races JRCQC, TKTTF, TTKSK and TRTTF whereas 24 lines showed susceptibility to the latter three races. Based on adult reaction, final disease severity and coefficient of infection data, Sixty six bread wheat lines and two cultivars Shorima and Huluka sustained final rust severity <30% and low ACI are acceptable for rust resistance breeding in wheat, However, 52 lines showed comparable resistance to Shorima or Hulluka are the priority materials to be used for developing resistant cultivars potentially combining non-race specific and race specific genes which is more durable than cultivars with major resistance gene effect and more efficient than sole adult plant resistance. Inherent resistance genes of these lines are unknown and warrant further description.

Registration of Oilseed Sunflower Germplasms RHA 461, RHA 462, RHA 463, HA 465, HA 466, HA 467, and RHA 468 with Diversity in Sclerotinia Resistance, Yield, and Other Traits

Sclerotinia head and stalk rots are among the most devastating diseases in sunflower (Helianthus annuus L.). Breeding for resistance to these diseases while maintaining or improving yield and quality is complicated by the quantitative inheritance of the resistance, for which there are few genes of major effect. The objective of this work was to provide new diversity to sunflower breeding organizations for yield and Sclerotinia resistance, together with other useful agronomic and end user traits. Four restorer germplasms, RHA 461 (Reg. No. GP‐337, PI 655012), RHA 462 (Reg. No. GP‐338; PI 655013), RHA 463 (Reg. No. GP‐339; PI 655014), and RHA 468 (Reg. No. GP‐341; PI 667184), and three maintainer germplasms, HA 465 (Reg. No. GP‐342; PI 670488), HA 466 (Reg. No. GP‐340; PI 667183), and HA 467 (Reg. No. GP‐343; PI 670489) were developed by the USDA‐ARS and the North Dakota Agricultural Experiment Station, Fargo, ND. Testcrosses with these germplasms had yield similar to high‐yielding commercial checks and Sclerotinia resistance similar to the highly resistant check ‘Northrup King 277’. Some of the lines also have high oleic acid in the seed oil, downy mildew resistance, and tolerance to imidazolinone herbicides. The lines are available for sunflower breeders to integrate into their breeding programs for additional diversity.

Loss of Color Pigmentation Is Maintained at High Frequency in a Monkey Flower Population.

Color polymorphisms have long been of evolutionary interest for their diverse roles, including mate choice, predator avoidance, and pollinator attraction. While color variation is often under strong selection, some taxa demonstrate unexpectedly high frequencies of presumed deleterious color forms. Here we show that a genetic variant underlying complete loss of anthocyanin pigmentation has risen to an unexpectedly high frequency of >0.2 in a natural population of the plant Mimulus guttatus. Decreased expression of MYB5 transcription factor is associated with unpigmented morphs. While the allele was found only in heterozygote adults in the wild, suggesting negative selection, experiments were unable to demonstrate a fitness cost for unpigmented plants, suggesting a cryptic selection pressure in the wild. However, life-history differences among morphs suggests that unpigmented individuals benefit from later flowering and clonal growth. Overall, our study highlights the complex interplay of factors maintaining variation in nature, even for genes of major effect.

Genetic evaluation for birth and conformation traits in dual-purpose Belgian Blue cattle using a mixed inheritance model.

The segregation of the causal mutation () in the muscular hypertrophy gene in dual-purpose Belgian Blue (dpBB) cattle is considered to result in greater calving difficulty (dystocia). Establishing adapted genetic evaluations might overcome this situation through efficient selection. However, the heterogeneity of dpBB populations at the locus implies separating the major gene and other polygenic effects in complex modeling. The use of mixed inheritance models may be an interesting option because they simultaneously assume both influences. A genetic evaluation in dpBB based on a mixed inheritance model was developed for birth and conformation traits: gestation length (GL), calving difficulty (CD), birth weight (BiW), and body conformation score (BC). A total of 27,362 animals having records were used for analyses. The total number of animals in the pedigree used to build the numerator relationship matrix was 62,617. Genotypes at the locus were available for 2,671 animals. Missing records at this locus were replaced with genotype probabilities. A total of 13,221 (48.3%) were registered as dpBB, 1,287 (4.7%) as beef Belgian Blue, and 12,854 (47.0%) were unknown. From those 13,221 dpBB animals, 650, 849, and 534 had double or single copies or no copy, respectively, of the causal mutation () in the muscular hypertrophy gene, whereas 11,188 had missing genotypes. This heterogeneity at the locus may be the reason for high variability in the studied traits, that is, high heritability estimates of 0.33, 0.30, 0.38, and 0.43 for GL, CD, BiW, and BC, respectively. In general, additive ( < 0.05) and dominance ( < 0.001) allele substitution for calves and dams had significant impact for all traits. The moderate coefficient of genetic variation (27.80%) and high direct heritability (0.28) for CD suggested genetic variability in dpBB and possible genetic improvement through selection. This variability has allowed dpBB breeders to successfully apply mass selection in the past. Genetic trend means from 1988 to 2016 showed that sire selection for CD within genotype was progressively applied by breeders. The selection intensity was more important for CD in double-muscled lines than in segregated lines. Our study illustrated the possible confusion caused by the use of major genes in selection and the importance of fitting appropriate models such as mixed inheritance models that combine polygenic and gene content information.

Exploring and Harnessing Haplotype Diversity to Improve Yield Stability in Crops.

In order to meet future food, feed, fiber, and bioenergy demands, global yields of all major crops need to be increased significantly. At the same time, the increasing frequency of extreme weather events such as heat and drought necessitates improvements in the environmental resilience of modern crop cultivars. Achieving sustainably increase yields implies rapid improvement of quantitative traits with a very complex genetic architecture and strong environmental interaction. Latest advances in genome analysis technologies today provide molecular information at an ultrahigh resolution, revolutionizing crop genomic research, and paving the way for advanced quantitative genetic approaches. These include highly detailed assessment of population structure and genotypic diversity, facilitating the identification of selective sweeps and signatures of directional selection, dissection of genetic variants that underlie important agronomic traits, and genomic selection (GS) strategies that not only consider major-effect genes. Single-nucleotide polymorphism (SNP) markers today represent the genotyping system of choice for crop genetic studies because they occur abundantly in plant genomes and are easy to detect. SNPs are typically biallelic, however, hence their information content compared to multiallelic markers is low, limiting the resolution at which SNP–trait relationships can be delineated. An efficient way to overcome this limitation is to construct haplotypes based on linkage disequilibrium, one of the most important features influencing genetic analyses of crop genomes. Here, we give an overview of the latest advances in genomics-based haplotype analyses in crops, highlighting their importance in the context of polyploidy and genome evolution, linkage drag, and co-selection. We provide examples of how haplotype analyses can complement well-established quantitative genetics frameworks, such as quantitative trait analysis and GS, ultimately providing an effective tool to equip modern crops with environment-tailored characteristics.

Perinatal risk factors in Tourette's and chronic tic disorders: a lesson from epidemiology.

Brander G, Rydell M, Kuja-Halkola R, et al. Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling omparison study [Epub ahead of print 2017 Mar 28]. Mol Psychiatry https://doi.org/10.1038/mp.2017.31 The role of perinatal factors in the pathophysiology of Tourette's and chronic tic disorders (TD/CTD) has been repeatedly suggested but never systematically analyzed. The recently published article by Brander and colleagues1 proposes a relationship between the occurrence of TD/CTD and several adverse perinatal events. The study cohort consisted of all live singleton births over a 30-year period in a single country. Follow-up was done over a 40-year period. It included a total of 3,026,861 individuals, 5597 of whom were diagnosed with TD/CTD during the study period. The main results showed that impaired fetal growth, preterm birth, breech presentation, and cesarean section were associated with a higher incidence of TD/CTD. A dose-response relationship also was observed, in which the higher the number of perinatal events, the higher the risk for TD/CTD. Maternal smoking during pregnancy also was suggested to be associated with the risk of TD/CTD in a dose-response manner; however, this could not be verified after sibling comparison analysis. During the current era of continuous genetic cause findings, evidence places TD/CTD among the most heritable, non-Mendelian neuropsychiatric diseases.2 Different studies found high population-based heritability estimates for this disorder3, 4; however, no unique, monogenic cause or ultimate associated risk gene of major effect has been identified, suggesting a polygenic origin for the disease or the possibility that epigenetic factors, such as perinatal hazards, may account for the substantial heterogeneity and complexity of TD/CTD.5 This study is particularly relevant because of its methodological design. It was designed as a population-based study, allowing for exclusion of potential biases and for sibling comparisons and posterior sensitivity analyses to minimize confounders. The first consequence of the study's interesting findings is clinical and relates to the need to address the presence of modifiable risk factors to prevent or reduce the occurrence of TD/CTD. This particular aspect also raises the question of whether these perinatal events are actually risk factors or the result of an ongoing process that generates such events that happen in the perinatal period, considering that impaired fetal growth, preterm birth, breech presentation, and the need for cesarean section can be the result of multiple hazards to the normal fetal development. The second learning point from the study by Brander and coworkers is how relevant epidemiological studies are to help clinicians and researchers clarify controversial hypothesis that arise from results produced by smaller studies or retrospective case series, like those addressing the pathophysiology of TD/CTD. To conclude, this interesting study increases our knowledge about perinatal risk factors for TD/CTD, creates a need for strategies that improve those events during the perinatal period to reduce the occurrence of TC/CTD, and serves as an excellent example of how epidemiological studies with clear and simple designs and analyses can add extremely important information to clinical practice. 1. Research Project: A. Conception, B. Organization, C. Execution; 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 3. Manuscript Preparation: A. Writing the First Draft, B. Review and Critique. V.B.: 1A, 1B, 1C, 3A, 3B J.E.A.: 1A, 1B, 1C, 3A, 3B Ethical Compliance Statement: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: The authors report no sources of funding and no conflicts of interest. Financial Disclosures for the previous 12 months: The authors report no sources of funding and no conflicts of interest.

Complex Coding and Regulatory Polymorphisms in a Restriction Factor Determine the Susceptibility of Drosophila to Viral Infection.

It is common to find that major-effect genes are an important cause of variation in susceptibility to infection. Here we have characterized natural variation in a gene called pastrel that explains over half of the genetic variance in susceptibility to the Drosophila C virus (DCV) in populations of Drosophila melanogaster. We found extensive allelic heterogeneity, with a sample of seven alleles of pastrel from around the world conferring four phenotypically distinct levels of resistance. By modifying candidate SNPs in transgenic flies, we show that the largest effect is caused by an amino acid polymorphism that arose when an ancestral threonine was mutated to alanine, greatly increasing resistance to DCV. Overexpression of the ancestral, susceptible allele provides strong protection against DCV; indicating that this mutation acted to improve an existing restriction factor. The pastrel locus also contains complex structural variation and cis-regulatory polymorphisms altering gene expression. We find that higher expression of pastrel is associated with increased survival after DCV infection. To understand why this variation is maintained in populations, we investigated genetic variation surrounding the amino acid variant that is causing flies to be resistant. We found no evidence of natural selection causing either recent changes in allele frequency or geographical variation in frequency, suggesting that this is an old polymorphism that has been maintained at a stable frequency. Overall, our data demonstrate how complex genetic variation at a single locus can control susceptibility to a virulent natural pathogen.

Phenotypic analysis of 303 multiplex families with common epilepsies.

Gene identification in epilepsy has mainly been limited to large families segregating genes of major effect and de novo mutations in epileptic encephalopathies. Many families that present with common non-acquired focal epilepsies and genetic generalized epilepsies remain unexplained. We assembled a cohort of 'genetically enriched' common epilepsies by collecting and phenotyping families containing multiple individuals with unprovoked seizures. We aimed to determine if specific clinical epilepsy features aggregate within families, and whether this segregation of phenotypes may constitute distinct 'familial syndromes' that could inform genomic analyses. Families with three or more individuals with unprovoked seizures were studied across multiple international centres. Affected individuals were phenotyped and classified according to specific electroclinical syndromes. Families were categorized based on syndromic groupings of affected family members, examined for pedigree structure and phenotypic patterns and, where possible, assigned specific familial epilepsy syndromes. A total of 303 families were assembled and analysed, comprising 1120 affected phenotyped individuals. Of the 303 families, 117 exclusively segregated generalized epilepsy, 62 focal epilepsy, and 22 were classified as genetic epilepsy with febrile seizures plus. Over one-third (102 families) were observed to have mixed epilepsy phenotypes: 78 had both generalized and focal epilepsy features within the same individual (n = 39), or within first or second degree relatives (n = 39). Among the genetic generalized epilepsy families, absence epilepsies were found to cluster within families independently of juvenile myoclonic epilepsy, and significantly more females were affected than males. Of the 62 familial focal epilepsy families, two previously undescribed familial focal syndrome patterns were evident: 15 families had posterior quadrant epilepsies, including seven with occipito-temporal localization and seven with temporo-parietal foci, and four families displayed familial focal epilepsy of childhood with multiple affected siblings that was suggestive of recessive inheritance. The findings suggest (i) specific patterns of syndromic familial aggregation occur, including newly recognized forms of familial focal epilepsy; (ii) although syndrome-specificity usually occurs in multiplex families, the one-third of families with features of both focal and generalized epilepsy is suggestive of shared genetic determinants; and (iii) patterns of features observed across families including pedigree structure, sex, and age of onset may hold clues for future gene identification. Such detailed phenotypic information will be invaluable in the conditioning and interpretation of forthcoming sequencing data to understand the genetic architecture and inter-relationships of the common epilepsy syndromes.

Quantitative trait loci in pepper control the effective population size of two RNA viruses at inoculation.

Infection of plants by viruses is a complex process involving several steps: inoculation into plant cells, replication in inoculated cells and plant colonization. The success of the different steps depends, in part, on the viral effective population size (Ne), defined as the number of individuals passing their genes to the next generation. During infection, the virus population will undergo bottlenecks, leading to drastic reductions in Ne and, potentially, to the loss of the fittest variants. Therefore, it is crucial to better understand how plants affect Ne. We aimed to (i) identify the plant genetic factors controlling Ne during inoculation, (ii) understand the mechanisms used by the plant to control Ne and (iii) compare these genetic factors with the genes controlling plant resistance to viruses. Ne was measured in a doubled-haploid population of Capsicum annuum. Plants were inoculated with either a Potato virus Y (PVY) construct expressing the green fluorescent protein or a necrotic variant of Cucumber mosaic virus (CMV). Newas assessed by counting the number of primary infection foci on cotyledons for PVY or the number of necrotic local lesions on leaves for CMV. The number of foci and lesions was correlated (r=0.57) and showed a high heritability (h2=0.93 for PVY and h2=0.98 for CMV). The Ne of the two viruses was controlled by both common quantitative trait loci (QTLs) and virus-specific QTLs, indicating the contribution of general and specific mechanisms. The PVY-specific QTL colocalizes with a QTL that reduces PVY accumulation and the capacity to break down a major-effect resistance gene.

Phenotypic diversity, major genes and production potential of local chickens and guinea fowl in Tamale, northern Ghana

ObjectiveOur study provides information on phenotypes of local chickens and guinea fowl and their body measures as well as on major genes in local chickens in northern Ghana.MethodsQualitative and morphometric traits were recorded on 788 local chickens and 394 guinea fowl in urban households in Tamale, Ghana.ResultsThe results showed considerable variation of color traits and numerous major genes in local chickens, while color variations and related genotypes in guinea fowl were limited. In local chickens, white was preferred for plumage, whereas dark colors were preferred for beak and shanks. More than half of the chickens carried at least one major gene, but the contributions of single gene carriers were low. All calculated allele frequencies were significantly lower than their expected Mendelian allele frequencies. We observed higher mean body weight and larger linear body measures in male as compared to female chickens. In female chickens, we detected a small effect of major genes on body weight and chest circumference. In addition, we found some association between feather type and plumage color. In guinea fowl, seven distinct plumage colors were observed, of which pearl grey pied and pearl grey were the most prevalent. Male pearl grey pied guinea fowl were inferior to pearl grey and white guinea fowl in terms of body weight, body length and chest circumference; their shank length was lower than that of pearl grey fowl.ConclusionConsiderable variation in qualitative traits of local chickens may be indicative of genetic diversity within local chicken populations, but major genes were rare. In contrast, phenotypic and genetic diversity in local guinea fowl is limited. Broader genetic diversity studies and evaluation of trait preferences of local poultry producers are required for the design of appropriate breeding programs.

Validação de marcadores moleculares associados à resistência à ferrugem marrom em cana-de-açúcar

RESUMO A ferrugem marrom causada pelo fungo Puccinia melanocephala é uma importante doença em cana-de-açúcar (Saccharum spp.) e está presente em praticamente todas as áreas de cultivo. Um gene de efeito maior, Bru1, foi descrito como fonte de resistência durável da cana-de-açúcar contra isolados de P. melanocephala. O objetivo deste estudo foi avaliar a eficiência de dois marcadores moleculares fortemente associados ao gene Bru1, R12H16 e 9O20-F4-RsaI, para predição da resistência genética à ferrugem marrom em variedades de cana-de-açúcar. Para tanto, foram utilizadas neste estudo 14 variedades RB, desenvolvidas pela RIDESA (Rede Interuniversitária para o Desenvolvimento do Setor Sucroenergético), as quais estão entre as 10 mais cultivadas na região Centro-Sul do Brasil no período de 1974 a 2015. Para avaliação da doença a campo foi conduzido um experimento em blocos casualizados com quatro repetições. A severidade da ferrugem marrom foi quantificada de acordo com escala diagramática que varia de 1 (mais resistente) a 9 (mais suscetível) e os dados obtidos foram analisados através de modelo misto linear generalizado (GLMM). Concomitantemente, foi extraído o DNA total das 14 variedades e, em seguida, foi realizada amplificação dos marcadores moleculares, que foram classificados em haplótipos. Do total de variedades, 12 não mostraram sintomas da doença e, através da análise via GLMM, apresentaram probabilidade de 99,35% de serem resistentes; destas, 91,66% foram haplótipo 1, ou seja, tiveram a presença de ambos os marcadores associados ao gene Bru1. Portanto, pode-se concluir que os marcadores moleculares R12H16 e 9O20-F4-RsaI foram altamente eficientes em predizer fenótipos resistentes e que provavelmente o gene Bru1 seja a principal fonte de resistência de cana-de-açúcar à ferrugem marrom nos campos comerciais do Brasil.

Advances in genomic strategies to improve growth and meat production traits in sheep: An overview

Growth and meat production traits (body weight at birth, 3-months and 6-months, eye muscle area, fat thickness, pre-weaning and post-weaning gains, average daily weight gain, chest girth, height at withers and shin circumference) are reviewed to know the relationship with the loci which are controlled by specific genes that are associated with these traits. Quantitative trait loci (QTL) for different body and carcass weight traits are identified. Chromosomes 1, 2, 3, 4, 5, 6, 16, 18 and 20 are considered as candidate genomic regions for body weight and some major gene effects like transferrin gene on chromosome 1, Belgium Texel double muscling and myostatin (MSTN) gene on chromosome 2, growth effect around insulin-like growth factor 1 (IGF-1) on chromosome 3, calpastatin gene on chromosome 5, leptin gene on chromosome 4, Booroola fecundity gene on chromosome 6, growth hormone receptor (GHR) gene in chromosome 16, callipyge effect and carawell muscle hypertrophy on chromosome 18 and MHC complex on chromosome 20 have been identified. High-throughput genotyping and next-generation sequencing technologies are the advanced techniques for the creation of the high-density SNP array as a tool for the genomic analysis of domestic animals. Genome-wide association studies (GWAS) and genomic selection are the ultimate use of SNP array for the improvement of economically important traits. Hence, genome-wide sequencing is an advanced tool which may help in better selection of animal genetic resources. It may be used for applying molecular breeding strategies in genetic improvement programmes oflivestock.