A selective sweep containing the insulin-like growth factor 1 (IGF1) gene is associated with size variation in domestic dogs. Intron 2 of IGF1 contains a SINE element and single nucleotide polymorphism (SNP) found in all small dog breeds that is almost entirely absent from large breeds. In this study, we surveyed a large sample of grey wolf populations to better understand the ancestral pattern of variation at IGF1 with a particular focus on the distribution of the small dog haplotype and its relationship to the origin of the dog.
We present DNA sequence data that confirms the absence of the derived small SNP allele in the intron 2 region of IGF1 in a large sample of grey wolves and further establishes the absence of a small dog associated SINE element in all wild canids and most large dog breeds. Grey wolf haplotypes from the Middle East have higher nucleotide diversity suggesting an origin there. Additionally, PCA and phylogenetic analyses suggests a closer kinship of the small domestic dog IGF1 haplotype with those from Middle Eastern grey wolves.
The absence of both the SINE element and SNP allele in grey wolves suggests that the mutation for small body size post-dates the domestication of dogs. However, because all small dogs possess these diagnostic mutations, the mutations likely arose early in the history of domestic dogs. Our results show that the small dog haplotype is closely related to those in Middle Eastern wolves and is consistent with an ancient origin of the small dog haplotype there. Thus, in concordance with past archeological studies, our molecular analysis is consistent with the early evolution of small size in dogs from the Middle East.
See associated opinion by Driscoll and Macdonald: http://jbiol.com/content/9/2/10
The largest genetic study to date of morphology in domestic dogs identifies genes
controlling nearly 100 morphological traits and identifies important trends in
phenotypic variation within this species.
Domestic dogs exhibit tremendous phenotypic diversity, including a greater
variation in body size than any other terrestrial mammal. Here, we generate a
high density map of canine genetic variation by genotyping 915 dogs from 80
domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across
60,968 single-nucleotide polymorphisms (SNPs). Coupling this genomic resource
with external measurements from breed standards and individuals as well as
skeletal measurements from museum specimens, we identify 51 regions of the dog
genome associated with phenotypic variation among breeds in 57 traits. The
complex traits include average breed body size and external body dimensions and
cranial, dental, and long bone shape and size with and without allometric
scaling. In contrast to the results from association mapping of quantitative
traits in humans and domesticated plants, we find that across dog breeds, a
small number of quantitative trait loci (≤3) explain the majority of
phenotypic variation for most of the traits we studied. In addition, many
genomic regions show signatures of recent selection, with most of the highly
differentiated regions being associated with breed-defining traits such as body
size, coat characteristics, and ear floppiness. Our results demonstrate the
efficacy of mapping multiple traits in the domestic dog using a database of
genotyped individuals and highlight the important role human-directed selection
has played in altering the genetic architecture of key traits in this important
Dogs offer a unique system for the study of genes controlling morphology. DNA
from 915 dogs from 80 domestic breeds, as well as a set of feral dogs, was
tested at over 60,000 points of variation and the dataset analyzed using novel
methods to find loci regulating body size, head shape, leg length, ear position,
and a host of other traits. Because each dog breed has undergone strong
selection by breeders to have a particular appearance, there is a strong
footprint of selection in regions of the genome that are important for
controlling traits that define each breed. These analyses identified new regions
of the genome, or loci, that are important in controlling body size and shape.
Our results, which feature the largest number of domestic dogs studied at such a
high level of genetic detail, demonstrate the power of the dog as a model for
finding genes that control the body plan of mammals. Further, we show that the
remarkable diversity of form in the dog, in contrast to some other species
studied to date, appears to have a simple genetic basis dominated by genes of
The worldwide dog population is fragmented into >350 domestic breeds. Breeds share a common ancestor, the gray wolf. The intense artificial selection imposed by humans to develop breeds with particular behaviors and phenotypic traits has occurred primarily in the last 200–300 years. As a result, the number of genes controlling the major differences in body size, leg length, head shape, etc. that define each dog is small, and genetically tractable. This is in comparison to many human complex traits where small amounts of variance are controlled by literally hundreds of genes. We have been interested in disentangling the genetic mechanisms controlling breed-defining morphological traits in the domestic dog. The structure of the dog population, comprised large numbers of pure breeding populations, makes this task surprisingly doable. In this review, we summarize recent work on the genetics of body size, leg length and skull shape, while setting the stage for tackling other traits. It is our expectation that these results will contribute to a better understanding of mammalian developmental processes overall.
Domestic dog breeds have undergone intense selection for a variety of morphologic features, including size. Among small-dog breeds, defined as those averaging less than ~15 in. at the withers, there remains still considerable variation in body size. Yet essentially all such dogs are fixed for the same allele at the insulin-like growth factor 1 gene, which we and others previously found to be a size locus of large effect. In this study we sought to identify additional genes that contribute to tiny size in dogs using an association scan with the single nucleotide polymorphism (SNP) dataset CanMap, in which 915 purebred dogs were genotyped at 60,968 SNP markers. Our strongest association for tiny size (defined as breed-average height not more than 10 in. at the withers) was on canine chromosome 3 (p = 1.9 × 10−70). Fine mapping revealed a nonsynonymous SNP at chr3:44,706,389 that changes a highly conserved arginine at amino acid 204 to histidine in the insulin-like growth factor 1 receptor (IGF1R). This mutation is predicted to prevent formation of several hydrogen bonds within the cysteine-rich domain of the receptor’s ligand-binding extracellular subunit. Nine of 13 tiny dog breeds carry the mutation and many dogs are homozygous for it. This work underscores the central importance of the IGF1 pathway in controlling the tremendous size diversity of dogs.
The turkey (Meleagris gallopavo) is an important agricultural species and the second largest contributor to the world’s poultry meat production. Genetic improvement is attributed largely to selective breeding programs that rely on highly heritable phenotypic traits, such as body size and breast muscle development. Commercial breeding with small effective population sizes and epistasis can result in loss of genetic diversity, which in turn can lead to reduced individual fitness and reduced response to selection. The presence of genomic diversity in domestic livestock species therefore, is of great importance and a prerequisite for rapid and accurate genetic improvement of selected breeds in various environments, as well as to facilitate rapid adaptation to potential changes in breeding goals. Genomic selection requires a large number of genetic markers such as e.g. single nucleotide polymorphisms (SNPs) the most abundant source of genetic variation within the genome.
Alignment of next generation sequencing data of 32 individual turkeys from different populations was used for the discovery of 5.49 million SNPs, which subsequently were used for the analysis of genetic diversity among the different populations. All of the commercial lines branched from a single node relative to the heritage varieties and the South Mexican turkey population. Heterozygosity of all individuals from the different turkey populations ranged from 0.17-2.73 SNPs/Kb, while heterozygosity of populations ranged from 0.73-1.64 SNPs/Kb. The average frequency of heterozygous SNPs in individual turkeys was 1.07 SNPs/Kb. Five genomic regions with very low nucleotide variation were identified in domestic turkeys that showed state of fixation towards alleles different than wild alleles.
The turkey genome is much less diverse with a relatively low frequency of heterozygous SNPs as compared to other livestock species like chicken and pig. The whole genome SNP discovery study in turkey resulted in the detection of 5.49 million putative SNPs compared to the reference genome. All commercial lines appear to share a common origin. Presence of different alleles/haplotypes in the SM population highlights that specific haplotypes have been selected in the modern domesticated turkey.
Clinical data from 72 dog breeds of varying size and life expectancy were grouped according to breed body mass and tested for prevalence at ages 4 to 5, ages 7 to 10, and lifetime incidence of non-hereditary, age-related cataract (ARC). The incidence of ARC was found to be directly related to the relative life expectancies in the breed groups: The smallest dog breeds had a lower ARC prevalence between ages 4 and 5 than mid-size breeds and these, in turn, a lower prevalence than the giant breeds. A similar sequence was evident for ages 7 to 10 and for overall lifetime incidence of ARC. These differences became more significant when comparing small and giant breeds only. We could also confirm the inverse relationship between body size and life expectancy in these same sets of dog breeds. Our results show that body size, life expectancy, and ARC incidence are interrelated in dogs. Given that ARC has been shown to be at least partially caused by oxidative damage to lens epithelial cells and the internal lens, we suggest that it can be considered not only as a general biomarker for life expectancy in the canine and possibly other species, but also for the systemic damages produced by reactive oxygen species. This suggests new approaches to examine the gene expression pathways affecting the above-noted linkages.
Dog; Age-related cataract; Breeds; Size; Life span
Genomic structure in a global collection of domesticated sheep reveals a history of artificial selection for horn loss and traits relating to pigmentation, reproduction, and body size.
Through their domestication and subsequent selection, sheep have been adapted to thrive in a diverse range of environments. To characterise the genetic consequence of both domestication and selection, we genotyped 49,034 SNP in 2,819 animals from a diverse collection of 74 sheep breeds. We find the majority of sheep populations contain high SNP diversity and have retained an effective population size much higher than most cattle or dog breeds, suggesting domestication occurred from a broad genetic base. Extensive haplotype sharing and generally low divergence time between breeds reveal frequent genetic exchange has occurred during the development of modern breeds. A scan of the genome for selection signals revealed 31 regions containing genes for coat pigmentation, skeletal morphology, body size, growth, and reproduction. We demonstrate the strongest selection signal has occurred in response to breeding for the absence of horns. The high density map of genetic variability provides an in-depth view of the genetic history for this important livestock species.
During the process of domestication, mankind recruited animals from the wild into a captive environment, changing their morphology, behaviour, and genetics. In the case of sheep, domestication and subsequent selection by their animal handlers over thousands of years has produced a spectrum of breeds specialised for the production of wool, milk, and meat. We sought to use this population history to search for the genes that directly underpin phenotypic variation. We collected DNA from 2,819 sheep, belonging to 74 breeds sampled from around the world, and assessed the genotype of each animal at nearly 50,000 locations across the genome. Our results show that sheep breeds have maintained high levels of genetic diversity, in contrast to other domestic animals such as dogs. We also show that particular regions of the genome contain strong evidence for accelerated change in response to artificial selection. The most prominent example was identified in response to breeding for the absence of horns, a trait now common across many modern breeds. Furthermore, we demonstrate that other genomic regions under selection in sheep contain genes controlling pigmentation, reproduction, and body size.
Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2
SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pacreatitis.
association; canine; disease; longevity; morphology; QTL
The tendency for male-larger sexual size dimorphism (SSD) to scale with body size – a pattern termed Rensch's rule – has been empirically supported in many animal lineages. Nevertheless, its theoretical elucidation is a subject of debate. Here, we exploited the extreme morphological variability of domestic dog (Canis familiaris) to gain insights into evolutionary causes of this rule.
We studied SSD and its allometry among 74 breeds ranging in height from less than 19 cm in Chihuahua to about 84 cm in Irish wolfhound. In total, the dataset included 6,221 individuals. We demonstrate that most dog breeds are male-larger, and SSD in large breeds is comparable to SSD of their wolf ancestor. Among breeds, SSD becomes smaller with decreasing body size. The smallest breeds are nearly monomorphic.
SSD among dog breeds follows the pattern consistent with Rensch's rule. The variability of body size and corresponding changes in SSD among breeds of a domestic animal shaped by artificial selection can help to better understand processes leading to emergence of Rensch's rule.
The extraordinary phenotypic diversity of dog breeds has been sculpted by a unique population history accompanied by selection for novel and desirable traits. Here we perform a comprehensive analysis using multiple test statistics to identify regions under selection in 509 dogs from 46 diverse breeds using a newly developed high-density genotyping array consisting of >170,000 evenly spaced SNPs. We first identify 44 genomic regions exhibiting extreme differentiation across multiple breeds. Genetic variation in these regions correlates with variation in several phenotypic traits that vary between breeds, and we identify novel associations with both morphological and behavioral traits. We next scan the genome for signatures of selective sweeps in single breeds, characterized by long regions of reduced heterozygosity and fixation of extended haplotypes. These scans identify hundreds of regions, including 22 blocks of homozygosity longer than one megabase in certain breeds. Candidate selection loci are strongly enriched for developmental genes. We chose one highly differentiated region, associated with body size and ear morphology, and characterized it using high-throughput sequencing to provide a list of variants that may directly affect these traits. This study provides a catalogue of genomic regions showing extreme reduction in genetic variation or population differentiation in dogs, including many linked to phenotypic variation. The many blocks of reduced haplotype diversity observed across the genome in dog breeds are the result of both selection and genetic drift, but extended blocks of homozygosity on a megabase scale appear to be best explained by selection. Further elucidation of the variants under selection will help to uncover the genetic basis of complex traits and disease.
There are hundreds of dog breeds that exhibit massive differences in appearance and behavior sculpted by tightly controlled selective breeding. This large-scale natural experiment has provided an ideal resource that geneticists can use to search for genetic variants that control these differences. With this goal, we developed a high-density array that surveys variable sites at more than 170,000 positions in the dog genome and used it to analyze genetic variation in 46 breeds. We identify 44 chromosomal regions that are extremely variable between breeds and are likely to control many of the traits that vary between them, including curly tails and sociality. Many other regions also bear the signature of strong artificial selection. We characterize one such region, known to associate with body size and ear type, in detail using “next-generation” sequencing technology to identify candidate mutations that may control these traits. Our results suggest that artificial selection has targeted genes involved in development and metabolism and that it may have increased the incidence of disease in dog breeds. Knowledge of these regions will be of great importance for uncovering the genetic basis of variation between dog breeds and for finding mutations that cause disease.
Myxomatous mitral valve disease (MMVD) is the most commonly diagnosed cardiovascular disease in the dog accounting for more than 70% of all cardiovascular disease in dogs. As are most canine diseases with genetic underpinnings, risk of MMVD is greatly increased in a subset of breeds. What is uncommon is that the vast majority of the breeds at elevated risk for MMVD are small or toy breeds with average adult weights under 9 kg. These breeds appear to have little in common other than their diminutive size. In the following review we propose a number of mechanisms by which relatively unrelated small breeds may have developed a predisposition for chronic valvular disorders. Although factors such as age are key in the expression of MMVD, taking a comprehensive look at the commonalities, as well as the differences, between the susceptible breeds may assist in finding the causal variants responsible for MMVD and translating them to improved treatments for both dogs and humans.
Canine genetics; degenerative valve disease; canine phenotype; dog breeds
Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait.
As a result of selective breeding practices, modern dogs display a multitude of head shapes. Breeds such as the Pug and Bulldog popularize one of these morphologies, termed “brachycephaly.” A short, upward-pointing snout, a massive and rounded head, and an underbite typify brachycephalic breeds. Here, we have coupled the phenotypes collected from museum skulls with the genotypes collected from dogs and identified five regions of the dog genome that are associated with canine brachycephaly. Fine mapping at one of these regions revealed a causal mutation in the gene BMP3. Bmp3's role in regulating cranial development is evolutionarily ancient, as zebrafish require its function to generate a normal craniofacial morphology. Our data begin to expose the genetic mechanisms unknowingly employed by breeders to create and diversify the cranial shape of dogs.
Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1–2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a ‘breeding value’ that could improve the accuracy of predicting a dog’s hip conformation.
Canine hip dysplasia; Genome wide screen; Microsatellites; Single nucleotide polymorphisms (SNP); Breeding values
Using 27 body measurements, we have identified 13 breed-defining metrics for 109 of 159 domestic dog breeds, most of which are recognized by the American Kennel Club (AKC). The data set included 1,155 dogs at least 1 year old (average 5.4 years), and for 53 breed populations, complete measurement data were collected from at least three males and three females. We demonstrate, first, that AKC breed standards are rigorously adhered to for most domestic breeds with little variation observed within breeds. Second, Rensch’s rule, which describes a scaling among taxa such that sexual dimorphism is greater among larger species if males are the larger sex, with less pronounced differences in male versus female body size in smaller species, is not maintained in domestic dog breeds because the proportional size difference between males and females of small and large breeds is essentially the same. Finally, principal components (PCs) analysis describes both the overall body size (PC1) and the shape (length versus width) of the skeleton (PC2). That the integrity of the data set is sufficiently rich to discern PCs has strong implications for mapping studies, suggesting that individual measurements may not be needed for genetic studies of morphologic traits, particularly in the case of breed-defining traits that are typically under strong selection. Rather, phenotypes derived from data sets such as these, collected at a fraction of the effort and cost, may be used to direct whole-genome association studies aimed at understanding the genetic basis of fixed morphologic phenotypes defining distinct dog breeds.
Horse body size varies greatly due to intense selection within each breed. American Miniatures are less than one meter tall at the withers while Shires and Percherons can exceed two meters. The genetic basis for this variation is not known. We hypothesize that the breed population structure of the horse should simplify efforts to identify genes controlling size. In support of this, here we show with genome-wide association scans (GWAS) that genetic variation at just four loci can explain the great majority of horse size variation. Unlike humans, which are naturally reproducing and possess many genetic variants with weak effects on size, we show that horses, like other domestic mammals, carry just a small number of size loci with alleles of large effect. Furthermore, three of our horse size loci contain the LCORL, HMGA2 and ZFAT genes that have previously been found to control human height. The LCORL/NCAPG locus is also implicated in cattle growth and HMGA2 is associated with dog size. Extreme size diversification is a hallmark of domestication. Our results in the horse, complemented by the prior work in cattle and dog, serve to pinpoint those very few genes that have played major roles in the rapid evolution of size during domestication.
In canine genetics, the impact of population structure on whole genome association studies is typically addressed by sampling approximately equal numbers of cases and controls from dogs of a single breed, usually from the same country or geographic area. However one way to increase the power of genetic studies is to sample individuals of the same breed but from different geographic areas, with the expectation that independent meiotic events will have shortened the presumed ancestral haplotype around the mutation differently. Little is known, however, about genetic variation among dogs of the same breed collected from different geographic regions.
In this report, we address the magnitude and impact of genetic diversity among common breeds sampled in the U.S. and Europe. The breeds selected, including the Rottweiler, Bernese mountain dog, flat-coated retriever, and golden retriever, share susceptibility to a class of soft tissue cancers typified by malignant histiocytosis in the Bernese mountain dog. We genotyped 722 SNPs at four unlinked loci (between 95 and 271 per locus) on canine chromosome 1 (CFA1). We showed that each population is characterized by distinct genetic diversity that can be correlated with breed history. When the breed studied has a reduced intra-breed diversity, the combination of dogs from international locations does not increase the rate of false positives and potentially increases the power of association studies. However, over-sampling cases from one geographic location is more likely to lead to false positive results in breeds with significant genetic diversity.
These data provide new guidelines for association studies using purebred dogs that take into account population structure.
The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60–100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480–3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage.
Canis familiaris; domestic dog; domestication; mitochondrial DNA; spitz-type breeds
The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143) of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data.
Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds.
A review of mtDNA haplotypes in dogs across the world revealed that: (a) breeds tend to display haplotypes belonging to different haplogroups; (b) haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c) haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d) genetic distances between breeds do not correlate with geography.
MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal) and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog) and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the Azores Cattle Dog descended maternally from Northern European dogs rather than Portuguese mainland dogs. A review of published mtDNA haplotypes identified thirteen non-Portuguese breeds with sufficient data for comparison. Comparisons between these thirteen breeds, and the four Portuguese breeds, demonstrated widespread haplotype sharing, with the greatest diversity among Asian dogs, in accordance with the central role of Asia in canine domestication.
The number of vertebrae in pigs varies and is associated with body size. Wild boars have 19 vertebrae, but European commercial breeds for pork production have 20 to 23 vertebrae. We previously identified two quantitative trait loci (QTLs) for number of vertebrae on Sus scrofa chromosomes (SSC) 1 and 7, and reported that an orphan nuclear receptor, NR6A1, was located at the QTL on SSC1. At the NR6A1 locus, wild boars and Asian local breed pigs had the wild-type allele and European commercial-breed pigs had an allele associated with increased numbers of vertebrae (number-increase allele).
Here, we performed a map-based study to define the other QTL, on SSC7, for which we detected genetic diversity in European commercial breeds. Haplotype analysis with microsatellite markers revealed a 41-kb conserved region within all the number-increase alleles in the present study. We also developed single nucleotide polymorphisms (SNPs) in the 450-kb region around the QTL and used them for a linkage disequilibrium analysis and an association study in 199 independent animals. Three haplotype blocks were detected, and SNPs in the 41-kb region presented the highest associations with the number of vertebrae. This region encodes an uncharacterized hypothetical protein that is not a member of any other known gene family. Orthologs appear to exist not only in mammals but also birds and fish. This gene, which we have named vertnin (VRTN) is a candidate for the gene associated with variation in vertebral number. In pigs, the number-increase allele was expressed more abundantly than the wild-type allele in embryos. Among candidate polymorphisms, there is an insertion of a SINE element (PRE1) into the intron of the Q allele as well as the SNPs in the promoter region.
Genetic diversity of VRTN is the suspected cause of the heterogeneity of the number of vertebrae in commercial-breed pigs, so the polymorphism information should be directly useful for assessing the genetic ability of individual animals. The number-increase allele of swine VRTN was suggested to add an additional thoracic segment to the animal. Functional analysis of VRTN may provide novel findings in the areas of developmental biology.
Advances in genome technology have facilitated a new understanding of the historical and genetic processes crucial to rapid phenotypic evolution under domestication1,2. To understand the process of dog diversification better, we conducted an extensive genome-wide survey of more than 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf. Here we show that dog breeds share a higher proportion of multi-locus haplotypes unique to grey wolves from the Middle East, indicating that they are a dominant source of genetic diversity for dogs rather than wolves from east Asia, as suggested by mitochondrial DNA sequence data3. Furthermore, we find a surprising correspondence between genetic and phenotypic/functional breed groupings but there are exceptions that suggest phenotypic diversification depended in part on the repeated crossing of individuals with novel phenotypes. Our results show that Middle Eastern wolves were a critical source of genome diversity, although interbreeding with local wolf populations clearly occurred elsewhere in the early history of specific lineages. More recently, the evolution of modern dog breeds seems to have been an iterative process that drew on a limited genetic toolkit to create remarkable phenotypic diversity.
An inherited basis for congenital extrahepatic portosystemic shunts (EHPSS) has been demonstrated in several small dog breeds. If in general both portocaval and porto-azygous shunts occur in breeds predisposed to portosystemic shunts then this could indicate a common genetic background. This study was performed to determine the distribution of extrahepatic portocaval and porto-azygous shunts in purebred dog populations.
Data of 135 client owned dogs diagnosed with EHPSS at the Faculty of Veterinary Medicine of Utrecht University from 2001 – 2010 were retrospectively analyzed. The correlation between shunt localization, sex, age, dog size and breed were studied. The study group consisted of 54 males and 81 females from 24 breeds. Twenty-five percent of dogs had porto-azygous shunts and 75% had portocaval shunts. Of the dogs with porto-azygous shunts only 27% was male (P = 0.006). No significant sex difference was detected in dogs with a portocaval shunt. Both phenotypes were present in almost all breeds represented with more than six cases. Small dogs are mostly diagnosed with portocaval shunts (79%) whereas both types are detected. The age at diagnosis in dogs with porto-azygous shunts was significantly higher than that of dogs with portocaval shunts (P < 0.001).
The remarkable similarity of phenotypic variation in many dog breeds may indicate common underlying genes responsible for EHPSS across breeds. The subtype of EHPSS could be determined by a minor genetic component or modulating factors during embryonic development.
Modern dog breeds display traits that are either breed-specific or shared by a few breeds as a result of genetic bottlenecks during the breed creation process and artificial selection for breed standards. Selective sweeps in the genome result from strong selection and can be detected as a reduction or elimination of polymorphism in a given region of the genome.
Extended regions of homozygosity, indicative of selective sweeps, were identified in a genome-wide scan dataset of 25 Boxers from the United Kingdom genotyped at ~20,000 single-nucleotide polymorphisms (SNPs). These regions were further examined in a second dataset of Boxers collected from a different geographical location and genotyped using higher density SNP arrays (~170,000 SNPs). A selective sweep previously associated with canine brachycephaly was detected on chromosome 1. A novel selective sweep of over 8 Mb was observed on chromosome 26 in Boxer and for a shorter region in English and French bulldogs. It was absent in 171 samples from eight other dog breeds and 7 Iberian wolf samples. A region of extended increased heterozygosity on chromosome 9 overlapped with a previously reported copy number variant (CNV) which was polymorphic in multiple dog breeds.
A selective sweep of more than 8 Mb on chromosome 26 was identified in the Boxer genome. This sweep is likely caused by strong artificial selection for a trait of interest and could have inadvertently led to undesired health implications for this breed. Furthermore, we provide supporting evidence for two previously described regions: a selective sweep on chromosome 1 associated with canine brachycephaly and a CNV on chromosome 9 polymorphic in multiple dog breeds.
The association of IGF-I gene polymorphisms with certain traits in 708 individuals of two Chinese dairy-goat breeds (Guanzhong and Xinong Saanen) was investigated. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing methods were employed in screening for genetic variation. Two novel mutations were detected in the 5'-flanking region and in intron 4 of IGF-I gene, viz., g.1617 G > A and g.5752 G > C (accession D26119.2), respectively. The associations of the g.1617 G > A mutation with milk yield and the body size were not significant (p > 0.05). However, in the case of g.5752 G > C, Xinong Saanen dairy goats with the CG genotype presented longer bodies (p < 0.05). Chest circumference (p < 0.05) was larger in Guanzhong goats with the GG genotype. In Xinong Saanen dairy goats with the CC genotype, milk yields were significantly higher during the first and second lactations (p < 0.05). Hence, the g.5752 G > C mutation could facilitate association analysis and serve as a genetic marker for Chinese dairy-goat breeding and genetics.
IGF-I gene; dairy goat; milk yield; PCR- SSCP
The nematode Caenorhabditis elegans is central to research in molecular, cell, and developmental biology, but nearly all of this research has been conducted on a single strain. Comparatively little is known about the population genomic and evolutionary history of this species. We characterized C. elegans genetic variation by high-throughput selective sequencing of a worldwide collection of 200 wild strains, identifying 41,188 single nucleotide polymorphisms. Unexpectedly, C. elegans genome variation is dominated by a set of commonly shared haplotypes on four of the six chromosomes, each spanning many megabases. Population-genetic modeling shows that this pattern was generated by chromosome-scale selective sweeps that have reduced variation worldwide; at least one of these sweeps likely occurred in the past few hundred years. These sweeps, which we hypothesize to be a result of human activity, have dramatically reshaped the global C. elegans population in the recent past.
Retrotransposition of processed mRNAs is a frequent source of novel sequence acquired during the evolution of genomes. The vast majority of retroposed gene copies are inactive pseudogenes that rapidly acquire mutations that disrupt the reading frame, while precious few are conserved to become new genes. Utilizing a multi-breed association analysis in the domestic dog, we demonstrate that a recently acquired fgf4 retrogene causes chondrodysplasia, a short-legged phenotype that defines several common dog breeds including the dachshund, corgi and basset hound. The discovery that a single evolutionary event underlies a breed-defining phenotype for 19 diverse dog breeds demonstrates the importance of unique mutational events in constraining and directing phenotypic diversity in the domestic dog.