Population Genetic Features Research Articles

Population Genetic Features of Calving Interval of Holstein-Friesian Cows Bred in Hungary.

Calving interval (CI) data (N = 37,263) from 17,319 cows born 2008-2018 in six herds were assessed. The data were made available by the National Association of Hungarian Holstein Friesian Breeders in Hungary. The effects of some genetic and environmental factors, population genetic parameters, breeding value (BV) of sires, and phenotypic and genetic trends of the CI were estimated. The GLM method was used for studying different effects on the CI. BLUP animal model was used for heritability (h2) and BV estimation. Linear regression analyses were applied for the trend calculation. The mean of the CI was 412.2 ± 2.0 days. The h2 of the CI proved to be low (0.07 ± 0.01 and 0.08 ± 0.01). There were relatively high differences among the sires in the estimated BV. Based on the phenotypic trend calculation, the CI of cows showed decreasing direction by an average of 1.80 days per year (R2 = 0.94; p < 0.01). In the case of genetic trend calculation, the average BV of sires in the CI has decreased -4.94 and -0.31 days per year (R2 = 0.91 and 0.41; p < 0.01).

Epidermolysis Bullosa in the Republic of North Ossetia-Alania: Population Genetic Features, Challenges and Prospects on the Example of Two Clinical Cases

Epidermolysis Bullosa in the Republic of North Ossetia-Alania: Population Genetic Features, Challenges and Prospects on the Example of Two Clinical Cases

Long-Term Population Genetic Features of the Rhopilema nomadica Jellyfish from the Israeli Mediterranean Coasts

The rhizostomatid scyphozoan Rhopilema nomadica is one of the most notorious marine invasive species established in the eastern Mediterranean Sea. Using seven microsatellite loci, here, we examined the population genetic structures on 587 individual tissue samples collected from 21 sites along the Mediterranean coast of Israel over a period of 16 years. The results indicate unique microsatellite landscapes for all samples, which belong to a single unstructured population. The &gt;20 alleles found in most loci, low fixation index (F) values (average 0.106), and high heterozygosity (average 0.667) suggest random or assortative mating. Additionally, the low overall differentiation (Fst) values (0.043) and pairwise Fst values between the samples collected in different years indicated gene flow and random mating over the years, potentially due to the long-lasting podocytes, scyphistomae, and adults causing a population overlap between the sampled months/years. Likewise, analyses were conducted between seasons, sites, and early/intermediate/late periods of collecting years. These results support the previous analyses performed on the mitochondrial gene cytochrome oxidase subunit I (COI) sequences, altogether indicating a highly polymorphic single unstructured R. nomadica population in the Levant, possibly backed by independent introductions. The results hint to the existence of highly functional connectivity with a genetically highly diverse source population.

Evolution of knockdown resistance (kdr) mutations of Aedes aegypti and Aedes albopictus in Hainan Island and Leizhou Peninsula, China.

Aedes aegypti and Aedes albopictus are important vectors of human arboviruses, transmitting arboviral diseases such as yellow fever, dengue, chikungunya and Zika. These two mosquitoes coexist on Hainan Island and the Leizhou Peninsula in China. Over the past 40 years, the distribution of Ae. albopictus has gradually expanded in these areas, while the distribution of Ae. aegypti has declined dramatically mainly due to the ecological changes and some other factors such as heavy use of insecticide indoor based on endophagic bloodfeeding of the species. This study focused on the knockdown resistance (kdr) genes of both mosquitoes, investigated their mutations, and analyzed their haplotype and evolutionary diversity combined with population genetic features based on the ND4/ND5 genes to further elucidate the molecular mechanisms underlying the development of insecticide resistance in both mosquitoes. Three mutations, S989P, V1016G and F1534C, were found to be present in Ae. aegypti populations, and the three mutations occurred synergistically. Multiple mutation types (F1534C/S/L/W) of the F1534 locus are found in Ae. albopictus populations, with the three common mutations F1534C, F1534S and F1534L all having multiple independent origins. The F1534W (TTC/TGG) mutation is thought to have evolved from the F1534L (TTC/TTG) mutation. The F1534S (TTC/TCG) mutation has evolved from the F1534S (TTC/TCC) mutation. The most common form of mutation at the F1534 locus found in this study was S1534C, accounting for 20.97%, which may have evolved from the F1534C mutation. In addition, a new non-synonymous mutation M1524I and 28 synonymous mutations were identified in Ae. albopictus populations. Correlation analysis showed that the genetic diversity of Ae. aegypti and Ae. albopictus populations did not correlate with their kdr haplotype diversity (P>0.05), but strong gene flow between populations may have contributed to the evolution of the kdr gene. The study of kdr gene evolution in the two mosquito species may help to identify the evolutionary trend of insecticide resistance at an early stage and provide a theoretical basis for improving the efficiency of biological vector control and subsequent research into new insecticides.

Population genetic features of calving interval of the Limousin beef cattle breed in Hungary.

Variance, covariance components, heritability, breeding values (BV) and genetic trends in calving interval (CI) of the Limousin population in Hungary were evaluated. A total of 3,008 CI data of 779 cows from three herds in 1996-2016 were processed. For influencing effects GLM method, for population genetic parameters and BV estimation BLUP animal model, for trend analyses linear regression was applied. The average CI obtained was 378.8 ± 3.1 days. The variance distribution components of the phenotype were as follow: age of cow at calving 34.30%, season of calving 26.09%, year of calving 23.00%, sire 7.45%, herd 3.23%, sex of calf 0.33% and type of calving 0.30%. The heritability of CI proved to be low (h2 d = 0.04 ± 0.02 and 0.03 ± 0.02; h2 m = 0.01 ± 0.02). The repeatability was low (R= 0.03 ± 0.02). Based on the phenotypic trend calculation, the CI of cows decreased by an average of 0.60 days per year (R 2 = 0.19; P < 0.05). In case of genetic trend calculation, the average BV of sires in CI increased 0.07 and 0.17 days per year (R 2 = 0.23 and 0.27; P < 0.05).

Proximal spinal muscular atrophy 5q in the Republic of North Ossetia – Alania: population-genetic features, diagnostic problems and treatment prospects

This study presents the structure and population data of spinal muscular atrophy 5q in the Republic of North Ossetia – Alania. The number of newborns for the period 2000–2020 was 195 954, and the prevalence of spinal muscular atrophy 5q among newborns was 1:24 494, or 4.08 per 100.000. That corresponds to data on other populations of the Russian Federation and the world. We also describe intermediate results of the clinical efficacy of treatment of three spinal muscular atrophy 5q patients. Gene replacement therapy was used in two cases and combined pathogenetic and gene replacement therapy was used in the third case. No clinically significant decrease in the CHOP INTEND score from the baseline level was found in any patient during follow‑up. Clinical improvement was noted both during treatment with nusinersen and after administration of onasemnogene abeparvovec. Described clinical cases demonstrate the importance of early diagnosis and initiation of antisense oligonucleotide and/or gene replacement therapy, which is possible only when spinal muscular atrophy 5q is included in the neonatal screening program.

Genetic Diversity, Heteroplasmy, and Recombination in Mitochondrial Genomes of Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa.

Genetic variants of mitochondrial DNA at the individual (heteroplasmy) and population (polymorphism) levels provide insight into their roles in multiple cellular and evolutionary processes. However, owing to the paucity of genome-wide data at the within-individual and population levels, the broad patterns of these two forms of variation remain poorly understood. Here, we analyze 1,804 complete mitochondrial genome sequences from Daphnia pulex, Daphnia pulicaria, and Daphnia obtusa. Extensive heteroplasmy is observed in D. obtusa, where the high level of intraclonal divergence must have resulted from a biparental-inheritance event, and recombination in the mitochondrial genome is apparent, although perhaps not widespread. Global samples of D. pulex reveal remarkably low mitochondrial effective population sizes, <3% of those for the nuclear genome. In addition, levels of population diversity in mitochondrial and nuclear genomes are uncorrelated across populations, suggesting an idiosyncratic evolutionary history of mitochondria in D. pulex. These population-genetic features appear to be a consequence of background selection associated with highly deleterious mutations arising in the strongly linked mitochondrial genome, which is consistent with polymorphism and divergence data suggesting a predominance of strong purifying selection. Nonetheless, the fixation of mildly deleterious mutations in the mitochondrial genome also appears to be driving positive selection on genes encoded in the nuclear genome whose products are deployed in the mitochondrion.

Exploratory analysis of multi-trait coadaptations in light of population history.

During the process of range expansion, populations encounter a variety of environments. They respond to the local environments by modifying their mutually interacting traits. Common approaches of landscape analysis include first focusing on the genes that undergo diversifying selection or directional selection in response to environmental variation. To understand the whole history of populations, it is ideal to capture the history of their range expansion with reference to the series of surrounding environments and to infer the multitrait coadaptation. To this end, we propose a complementary approach; it is an exploratory analysis using up‐to‐date methods that integrate population genetic features and features of selection on multiple traits. First, we conduct correspondence analysis of site frequency spectra, traits, and environments with auxiliary information of population‐specific fixation index (F ST). This visualizes the structure and the ages of populations and helps infer the history of range expansion, encountered environmental changes, and selection on multiple traits. Next, we further investigate the inferred history using an admixture graph that describes the population split and admixture. Finally, principal component analysis of the selection on edge‐by‐trait (SET) matrix identifies multitrait coadaptation and the associated edges of the admixture graph. We introduce a newly defined factor loadings of environmental variables in order to identify the environmental factors that caused the coadaptation. A numerical simulation of one‐dimensional stepping‐stone population expansion showed that the exploratory analysis reconstructed the pattern of the environmental selection that was missed by analysis of individual traits. Analysis of a public dataset of natural populations of black cottonwood in northwestern America identified the first principal component (PC) coadaptation of photosynthesis‐ vs growth‐related traits responding to the geographical clines of temperature and day length. The second PC coadaptation of volume‐related traits suggested that soil condition was a limiting factor for aboveground environmental selection.

Detection and molecular characteristics of Rhytidodoides sp. (Digenea: Rhytidodidae) from the gall bladder of green sea turtles (Chelonia mydas) in the Ogasawara Islands, Japan.

Trematodes of the genus Rhytidodoides are parasitic in marine turtles. Of the already known species, Rhytidodoides similis Price, 1939, occurs especially in the gall bladder. In this study, we surveyed 73 green sea turtles (Chelonia mydas) in the Ogasawara Islands, Japan, and detected Rhytidodoides sp. from the gall bladders of 18 turtles. A detailed morphological analysis revealed that the forebody of Rhytidodoides sp. differed slightly in shape from that of R. similis. There has been no information on DNA sequences of the family Rhytidodidae. A molecular phylogeny based on 28S rDNA sequences of Rhytidodoides sp. and related taxa suggested that the Rhytidodidae is sister to the other families of Echinostomatoidea. The intraspecific diversity of Rhytidodoides sp. was examined by using DNA sequences of mitochondrial cytochrome c oxidase subunit 1 gene (COI). The population genetic features of the COI haplotypes demonstrated that Rhytidodoides sp. is highly diverse in the Ogasawara Islands. The DNA sequences determined in this study will contribute to the species identification of congeners and the taxonomic reconsideration of the Echinostomatoidea.

Long-term changes in population genetic features of a rapidly expanding marine invader: implication for invasion success

Large blooms of Rhopilema nomadica, a highly venomous rhizostamatid scyphozoan species introduced to the Mediterranean through the Suez Canal, have become ubiquitous in the summer and winter months along the Israeli coasts since the mid-1980s. This species has since spread across the eastern Mediterranean and was sighted as far west as Tunisia and Sardinia. For the past 12 years, we have studied changes in the mitochondrial COI haplotypes diversity of R. nomadica to investigate small scale fluctuactions of genetic diversity and to reveal possible genetic structuring of the fast spreading invader in the Eastern Mediterranean. The 1091 COI sequences analysed, revealed a highly diverse population displaying 89 haplotypes, 46 of which appeared as singletons, low frequency haplotypes. All the specimens analysed throughout the period belong to a single unstructured population. Though lacking data from the source population in the Red Sea, the high within-population diversity and the high diversity of COI haplotypes support the hypothesis of multiple introductions events, or an open corridor with a continuous influx of propagules. Tajima’s D and Fu’s Fst negative values and the increased numbers of COI singletons from early to late sampling periods, have verified that the Israeli population is characterized by a rapid expanding population. Further research is needed for the evaluation of COI diversity and patterns in R. nomadica populations across the eastern Mediterranean Sea and Red Sea, as well as any correlation of the high variability between COI locus and phenotypic diversity.

Genome–Phenome Wide Association in Maize and Arabidopsis Identifies a Common Molecular and Evolutionary Signature

Linking natural genetic variation to trait variation can help determine the functional roles ofdifferent genes. Variations of one or several traits are often assessed separately. High-throughput phenotyping and data mining can capture dozens or hundreds of traits from the same individuals. Here, we test the association between markers within a gene and many traits simultaneously. This genome–phenome wide association study (GPWAS) is both a multi-marker and multi-trait test. Genes identified using GPWAS with 260 phenotypic traits in maize were enriched for genes independently linked to phenotypic variation. Traits associated with classical mutants were consistent with reported phenotypes for mutant alleles. Genes linked to phenomic variation in maize using GPWAS shared molecular, population genetic, and evolutionary features with classical mutants in maize. Genes linked to phenomic variation in Arabidopsis using GPWAS are significantly enriched in genes with known loss-of-function phenotypes. GPWAS may be an effective strategy to identify genes in which loss-of-function alleles produce mutant phenotypes. The shared signatures present in classical mutants and genes identified using GPWAS may be markers for genes with a role in specifying plant phenotypes generally or pleiotropy specifically.

Functional and population genetic features of copy number variations in two dairy cattle populations

BackgroundCopy Number Variations (CNVs) are gain or loss of DNA segments that are known to play a role in shaping a wide range of phenotypes. In this study, we used two dairy cattle populations, Holstein Friesian and Jersey, to discover CNVs using the Illumina BovineHD Genotyping BeadChip aligned to the ARS-UCD1.2 assembly. The discovered CNVs were investigated for their functional impact and their population genetics features.ResultsWe discovered 14,272 autosomal CNVs, which were aggregated into 1755 CNV regions (CNVR) from 451 animals. These CNVRs together cover 2.8% of the bovine autosomes. The assessment of the functional impact of CNVRs showed that rare CNVRs (MAF < 0.01) are more likely to overlap with genes, than common CNVRs (MAF ≥ 0.05). The Population differentiation index (Fst) based on CNVRs revealed multiple highly diverged CNVRs between the two breeds. Some of these CNVRs overlapped with candidate genes such as MGAM and ADAMTS17 genes, which are related to starch digestion and body size, respectively. Lastly, linkage disequilibrium (LD) between CNVRs and BovineHD BeadChip SNPs was generally low, close to 0, although common deletions (MAF ≥ 0.05) showed slightly higher LD (r2 = ~ 0.1 at 10 kb distance) than the rest. Nevertheless, this LD is still lower than SNP-SNP LD (r2 = ~ 0.5 at 10 kb distance).ConclusionsOur analyses showed that CNVRs detected using BovineHD BeadChip arrays are likely to be functional. This finding indicates that CNVs can potentially disrupt the function of genes and thus might alter phenotypes. Also, the population differentiation index revealed two candidate genes, MGAM and ADAMTS17, which hint at adaptive evolution between the two populations. Lastly, low CNVR-SNP LD implies that genetic variation from CNVs might not be fully captured in routine animal genetic evaluation, which relies solely on SNP markers.

Population Structure, Taxonomy, and Genetic Features of Yersinia pestis Strains of the Central Asian Subspecies

On the basis of the data of phylogeographical analysis, strains of Yersinia pestis are divided into a number of phylogenetic branches, and in accordance with the traditionally used subspecies classification in the CIS countries, they are divided into five subspecies. We conducted a study of the population structure and genetic characteristics of strains belonging to the phylogenetic branch 0.PE4 and its strains of the Altai subspecies—0.PE4a (Russia, Mongolia), the Hissar subspecies—0.PE4h (Tajikistan), the Talas population—0.PE4t (Kyrgyzstan), and the microtus population—0.PE4m (China). The uniformity of phenotypic and genetic characteristics of strains of the 0.PE4 branch has been established and the necessity of their association into one subspecies, the Central Asian (Y. pestis subsp. central asiatica), has been substantiated. The dendrogram demonstrates the presence of four separate subclusters corresponding to four populations: 0.PE4a (Altai strains), 0.PE4h (Hissar strains), 0.PE4t (Talas strains), and 0.PE4m (microtus strains) in the composition of the 0.PE4 cluster, which we propose to allocate to four biovars of the Central Asian subspecies: Altai, Hissar, Talas, and Microtus. A number of mutations specific only to 0.PE4 strains were detected. A DNA target was found and a method for differentiating the Central Asian subspecies (strains avirulent for humans) from other strains of Y. pestis by Real-Time PCR was developed.

When new human-modified habitats favour the expansion of an amphibian pioneer species: Evolutionary history of the natterjack toad (Bufo calamita) in a coal basin.

Human activities affect microevolutionary dynamics by inducing environmental changes. In particular, land cover conversion and loss of native habitats decrease genetic diversity and jeopardize the adaptive ability of populations. Nonetheless, new anthropogenic habitats can also promote the successful establishment of emblematic pioneer species. We investigated this issue by examining the population genetic features and evolutionary history of the natterjack toad (Bufo [Epidalea] calamita) in northern France, where populations can be found in native coastal habitats and coalfield habitats shaped by European industrial history, along with an additional set of European populations located outside this focal area. We predicted contrasting patterns of genetic structure, with newly settled coalfield populations departing from migration-drift equilibrium. As expected, coalfield populations showed a mosaic of genetically divergent populations with short-range patterns of gene flow, and native coastal populations indicated an equilibrium state with an isolation-by-distance pattern suggestive of postglacial range expansion. However, coalfield populations exhibited (i) high levels of genetic diversity, (ii) no evidence of local inbreeding or reduced effective population size and (iii) multiple maternal mitochondrial lineages, a genetic footprint depicting independent colonization events. Furthermore, approximate Bayesian computations suggested several evolutionary trajectories from ancient isolation in glacial refugia during the Pleistocene, with biogeographical signatures of recent expansion probably confounded by human-mediated mixing of different lineages. From an evolutionary and conservation perspective, this study highlights the ecological value of industrial areas, provided that ongoing regional gene flow is ensured within the existing lineage boundaries.

Population genetics features for persistent, but transient, Botryllus schlosseri (Urochordata) congregations in a central Californian marina

The colonial tunicate Botryllus schlosseri is a globally distributed, invasive ascidian that has colonized the Californian coasts of the USA during the mid-late 1940s and has, since the late 1980s, spread north to Washington. This study analyzes the population genetic characteristics of transient populations residing at the Elkhorn Yacht-Club (EYC), in central California (seven sessions, 1996–2008), which suffered periodic catastrophes caused by episodic fresh-water floods and a single sampling session (in the year 2001) of five West-Coast populations using the mtDNA COI gene and five microsatellite markers. EYC microsatellite results were further compared with the closely situated but persistent population of the Santa Cruz Harbor (SCH) to understand the impact on EYC population regeneration processes after the 2005-flood catastrophe. All microsatellites were highly polymorphic, revealing a large number of unique alleles at different sampling dates. Whereas pairwise θ did not reveal significant differences between the EYC time-series samplings, the overall θ was significant, as it was between all the 2001 West Coast populations. The most likely cluster number was 3 for the EYC samples whereas two K values were obtained (2 and 5) for the 2001 samples. Tajima’s D and Fu’s/Fs tests did not reject the null hypothesis for COI neutral evolution, except for in the EYC-2000, 2007 and two 2001 samplings. The wide geographical range of the analyses has indicated that following the EYC 2005-flood catastrophe, newcomers could have originated from neighboring populations, from deep-water colonies that may have escaped the 2005 low salinity event, or less expectedly, from far away West-Coast populations, while revealing that the SCH population is the most probable source for the EYC population.

Forensic and population genetic characteristics of 62 X chromosome SNPs revealed by multiplex PCR and MALDI-TOF mass spectrometry genotyping in 4 North Eurasian populations.

X chromosome genetic markers are widely used in basic population genetic research as well as in forensic genetics. In this paper we analyze the genetic diversity of 62 X chromosome SNPs in 4 populations using multiplex genotyping based on multi-locus PCR and MALDI-TOF mass spectrometry, and report forensic and population genetic features of the panel of X-linked SNPs (XSNPid). Studied populations represent Siberian (Buryat and Khakas), North Asian (Khanty) and Central Asian (Kazakh) native people. Khanty, Khakas and Kazakh population demonstrate average gene diversity over 0.45. Only East Siberian Buryat population is characterized by lower average heterozygosity (0.436). AMOVA analysis of genetic structure reveals a relatively low but significant level of genetic differentiation in a group of 4 population studied (FST=0.023, p=0.0000). The XSNPid panel provides a very high discriminating power in each population. The combined probability of discrimination in females (PDf) for XSNPid panel ranged between populations from 0.99999999999999999999999982 in Khakas to 0.9999999999999999999999963 in Buryats. The combined discriminating power in males (PDm) varies from 0.999999999999999792 to 0.9999999999999999819. The developed multiplex set of X chromosome SNPs can be a useful tool for population genetic studies and for forensic identity and kinship testing.

Ecological and Lineage-Specific Factors Drive the Molecular Evolution of Rhodopsin in Cichlid Fishes.

The visual system in the colorful cichlid fishes from the African great lakes is believed to be important for their adaptive radiations. However, few studies have attempted to compare the visual system of radiating cichlid lineages with that of cichlids that have not undergone recent radiations. One such study published in this journal (Schott RK, Refvik SP, Hauser FE, López-Fernández H, Chang BSW. 2014. Divergent positive selection in rhodopsin from lake and riverine cichlid fishes. Mol Biol Evol. 31:1149-1165) found divergent selection on rhodopsin between African lacustrine and riverine cichlid species and riverine Neotropical cichlids, concluding that ecology drives the molecular evolution of this opsin. Here, we expand this analysis by incorporating rhodopsin sequences from Neotropical lacustrine cichlids and show that both ecology and phylogeny are important drivers of the molecular evolution of rhodopsin in cichlids. We found little overlap of sites under selection between African and Neotropical lineages and a faster rate of molecular evolution in African compared with Neotropical cichlids. These results support the notion that genetic or population genetic features particular to African cichlids contributed to their radiations.

Highly polymorphic microsatellite markers in two species, the invasive shore crabs Hemigrapsus sanguineus and Hemigrapsus takanoi (Decapoda, Varunidae)

Varunid crabs Hemigrapsus sanguineus and Hemigrapsus takanoi are species native from intertidal coastal areas in North-western Pacific and have become invasive along the Atlantic European coasts. To gain insights into population genetic features, we developed and characterized 16 (H. sanguineus) and 11 (H. takanoi) novel polymorphic microsatellite loci from next-generation sequencing. The number of alleles ranged from 2 to 20 for H. sanguineus, and from 8 to 21 for H. takanoi. Expected heterozygosity ranged from 0.470 to 0.947 and from 0.313 to 0.781, with mean multilocus Fis estimates suggesting rapid turnover of populations. Overall, these microsatellite markers showed very high levels of polymorphism that will facilitate population genetic studies devoted to track down the most likely sources of introduction.

HGPGD: the human gene population genetic difference database.

Demographic events such as migration, and evolutionary events like mutation and recombination, have contributed to the genetic variations that are found in the human genome. During the evolution and differentiation of human populations, different functional genes and pathways (a group of genes that act together to perform specific biological tasks) would have displayed different degrees of genetic diversity or evolutionary conservatism. To query the genetic differences of functional genes or pathways in populations, we have developed the human gene population genetic difference (HGPGD) database. Currently, 11 common population genetic features, 18,158 single human genes, 220 KEGG (Kyoto Encyclopedia of Genes and Genomes) human pathways and 4,639 Gene Ontology (GO) categories (3,269 in biological process; 862 in molecular function; and 508 in cellular component) are available in the HGPGD database. The 11 population genetic features are related mainly to three aspects: allele frequency, linkage disequilibrium pattern, and transferability of tagSNPs. By entering a list of Gene IDs, KEGG pathway IDs or GO category IDs and selecting a population genetic feature, users can search the genetic differences between pairwise HapMap populations. We hope that, when the researchers carry out gene-based, KEGG pathway-based or GO category-based research, they can take full account of the genetic differences between populations. The HGPGD database (V1.0) is available at http://www.bioapp.org/hgpgd.

A genome-wide analysis of 'Bounty' descendants implicates several novel variants in migraine susceptibility

Migraine is a common neurological disease with a complex genetic aetiology. The disease affects ~12% of the Caucasian population and females are three times more likely than males to be diagnosed. In an effort to identify loci involved in migraine susceptibility, we performed a pedigree-based genome-wide association study of the isolated population of Norfolk Island, which has a high prevalence of migraine. This unique population originates from a small number of British and Polynesian founders who are descendents of the Bounty mutiny and forms a very large multigenerational pedigree (Bellis et al.; Human Genetics, 124(5):543-5542, 2008). These population genetic features may facilitate disease gene mapping strategies (Peltonen et al.; Nat Rev Genet, 1(3):182-90, 2000. In this study, we identified a high heritability of migraine in the Norfolk Island population (h (2) = 0.53, P = 0.016). We performed a pedigree-based GWAS and utilised a statistical and pathological prioritisation approach to implicate a number of variants in migraine. An SNP located in the zinc finger protein 555 (ZNF555) gene (rs4807347) showed evidence of statistical association in our Norfolk Island pedigree (P = 9.6 × 10(-6)) as well as replication in a large independent and unrelated cohort with >500 migraineurs. In addition, we utilised a biological prioritisation to implicate four SNPs, in within the ADARB2 gene, two SNPs within the GRM7 gene and a single SNP in close proximity to a HTR7 gene. Association of SNPs within these neurotransmitter-related genes suggests a disrupted serotoninergic system that is perhaps specific to the Norfolk Island pedigree, but that might provide clues to understanding migraine more generally.