Microsatellites are polymorphic tracts of short tandem repeats with one to six base-pair (bp) motifs and are some of the most polymorphic variants in the genome. Using 6084 Icelandic parent-offspring ...trios we estimate 63.7 (95% CI: 61.9-65.4) microsatellite de novo mutations (mDNMs) per offspring per generation, excluding one bp repeats motifs (homopolymers) the estimate is 48.2 mDNMs (95% CI: 46.7-49.6). Paternal mDNMs occur at longer repeats than maternal ones, which are in turn larger with a mean size of 3.4 bp vs 3.1 bp for paternal ones. mDNMs increase by 0.97 (95% CI: 0.90-1.04) and 0.31 (95% CI: 0.25-0.37) per year of father's and mother's age at conception, respectively. Here, we find two independent coding variants that associate with the number of mDNMs transmitted to offspring; The minor allele of a missense variant (allele frequency (AF) = 1.9%) in MSH2, a mismatch repair gene, increases transmitted mDNMs from both parents (effect: 13.1 paternal and 7.8 maternal mDNMs). A synonymous variant (AF = 20.3%) in NEIL2, a DNA damage repair gene, increases paternally transmitted mDNMs (effect: 4.4 mDNMs). Thus, the microsatellite mutation rate in humans is in part under genetic control.
While the rare occurrence of child loss is accompanied by reduced life expectancy of parents in contemporary affluent populations, its impact in developing societies with high child mortality rates ...is unclear. We identified all parents in Iceland born 1800-1996 and compared the mortality rates of 47,711 parents who lost a child to those of their siblings (N = 126,342) who did not. The proportion of parents who experienced child loss decreased from 61.1% of those born 1800-1880 to 5.2% of those born after 1930. Child loss was consistently associated with increased rate of maternal, but not paternal, death before the age of 50 across all parent birth cohorts; the relative increase in maternal mortality rate ranged from 35% among mothers born 1800-1930 to 64% among mothers born after 1930. The loss of a child poses a threat to the survival of young mothers, even during periods of high infant mortality rates.
We present results from a genome-wide association study for variants associated with human pigmentation characteristics among 5,130 Icelanders, with follow-up analyses in 2,116 Icelanders and 1,214 ...Dutch individuals. Two coding variants in TPCN2 are associated with hair color, and a variant at the ASIP locus shows strong association with skin sensitivity to sun, freckling and red hair, phenotypic characteristics similar to those affected by well-known mutations in MC1R.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The persistence of common, heritable psychiatric disorders that reduce reproductive fitness is an evolutionary paradox. Here, we investigate the selection pressures on sequence variants that ...predispose to schizophrenia, autism, bipolar disorder, major depression and attention deficit hyperactivity disorder (ADHD) using genomic data from 150,656 Icelanders, excluding those diagnosed with these psychiatric diseases. Polygenic risk of autism and ADHD is associated with number of children. Higher polygenic risk of autism is associated with fewer children and older age at first child whereas higher polygenic risk of ADHD is associated with having more children. We find no evidence for a selective advantage of a high polygenic risk of schizophrenia or bipolar disorder. Rare copy-number variants conferring moderate to high risk of psychiatric illness are associated with having fewer children and are under stronger negative selection pressure than common sequence variants.
Rare missense mutations in the gene encoding coatomer subunit alpha (COPA) have recently been shown to cause autoimmune interstitial lung, joint and kidney disease, also known as COPA syndrome, under ...a dominant mode of inheritance.
Here we describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis. We performed whole-genome sequencing (WGS) of the three affected as well as three unaffected members of the family, and searched for rare genotypes associated with disease using 30,067 sequenced Icelanders as a reference population. We assessed all coding and splicing variants, prioritizing variants in genes known to cause interstitial lung disease. We detected a heterozygous missense mutation, p.Glu241Lys, in the COPA gene, private to the affected family members. The mutation occurred de novo in the paternal germline of the index case and was absent from 30,067 Icelandic genomes and 141,353 individuals from the genome Aggregation Database (gnomAD). The mutation occurs within the conserved and functionally important WD40 domain of the COPA protein.
This is the second report of the p.Glu241Lys mutation in COPA, indicating the recurrent nature of the mutation. The mutation was reported to co-segregate with COPA syndrome in a large family from the USA with five affected members, and classified as pathogenic. The two separate occurrences of the p.Glu241Lys mutation in cases and its absence from a large number of sequenced genomes confirms its role in the pathogenesis of the COPA syndrome.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Conventional wisdom suggests that occupational class plays a limited role in explaining vote choice in Iceland. In this paper, we argue that the death of class in Icelandic politics may be premature ...and that it still plays a role in structuring political preferences and party choice. While the importance of the traditional class cleavage may have declined to the point of irrelevance, we suggest that there is a new type of class voting in Iceland, containing both a vertical and a horizontal component. Furthermore, we argue that the Great Recession played a critical role in increasing the strength of class voting around this new class schema, both because of the conflict around economic issues it generated, but also because of its facilitation of the formation and success of new parties. We test our main hypotheses using multinomial logistic regression on data from the Icelandic National Election Study from 1999 to 2016 and apply a modified measure of cleavage strength, which we refer to as “Full Kappa”. Our results suggest that class voting is alive and well in Iceland and that its strength has increased following the Great Recession.
The Icelandic population has been sampled in many disease association studies, providing a strong motivation to understand the structure of this population and its ramifications for disease gene ...mapping. Previous work using 40 microsatellites showed that the Icelandic population is relatively homogeneous, but exhibits subtle population structure that can bias disease association statistics. Here, we show that regional geographic ancestries of individuals from Iceland can be distinguished using 292,289 autosomal single-nucleotide polymorphisms (SNPs). We further show that subpopulation differences are due to genetic drift since the settlement of Iceland 1100 years ago, and not to varying contributions from different ancestral populations. A consequence of the recent origin of Icelandic population structure is that allele frequency differences follow a null distribution devoid of outliers, so that the risk of false positive associations due to stratification is minimal. Our results highlight an important distinction between population differences attributable to recent drift and those arising from more ancient divergence, which has implications both for association studies and for efforts to detect natural selection using population differentiation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previous studies have reported that related human couples tend to produce more children than unrelated couples but have been unable to determine whether this difference is biological or stems from ...socioeconomic variables. Our results, drawn from all known couples of the Icelandic population born between 1800 and 1965, show a significant positive association between kinship and fertility, with the greatest reproductive success observed for couples related at the level of third and fourth cousins. Owing to the relative socioeconomic homogeneity of Icelanders, and the observation of highly significant differences in the fertility of couples separated by very fine intervals of kinship, we conclude that this association is likely to have a biological basis.
A genome is a mosaic of chromosome fragments from ancestors who existed some arbitrary number of generations earlier. Here, we reconstruct the genome of Hans Jonatan (HJ), born in the Caribbean in ...1784 to an enslaved African mother and European father. HJ migrated to Iceland in 1802, married and had two children. We genotyped 182 of his 788 descendants using single-nucleotide polymorphism (SNP) chips and whole-genome sequenced (WGS) 20 of them. Using these data, we reconstructed 38% of HJ's maternal genome and inferred that his mother was from the region spanned by Benin, Nigeria and Cameroon.
In recent years, political science has seen a boom in the use of sophisticated methodological tools for time series analysis. One such tool is the general error correction model (GECM), originally ...introduced to political scientists in the pages of this journal over 20 years ago (Durr 1992; Ostrom and Smith 1992) and re-introduced by De Boef and Keele (2008), who advocate its use for a wider set of time series data than previously considered appropriate. Their article has proven quite influential, with numerous papers justifying their methodological choices with reference to De Boef and Keele's contribution. Grant and Lebo (2016) take issue with the increasing use of the GECM in political science and argue that the methodology is widely misused and abused by practitioners. Given the recent surge of research conducted using error correction methods, there is every reason to take their suggestions seriously and provide a fuller discussion of the points they raise in their paper. The present symposium serves such a role. It consists of Grant and Lebo's critique, a detailed response by Keele, Linn, and Webb (2016b), and shorter comments by Esarey (2016), Freeman (2016), and Helgason (2016). Finally, Lebo and Grant (2016) and Keele, Linn, and Webb (2016a) reflect on the contributions made in the symposium, as well as discuss outstanding issues.
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