bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic insight into sick sinus syndrome
Authors: Thorolfsdottir Rosa B , Sveinbjornsson Gardar , Aegisdottir Hildur M , Benonisdottir Stefania , Stefansdottir Lilja , Ivarsdottir Erna V , Halldorsson Gisli H , Sigurdsson Jon K , Torp-Pedersen Christian , Weeke Peter E , Brunak Søren , Westergaard David , Pedersen Ole B , Sorensen Erik , Nielsen Kaspar R , Burgdorf Kristoffer S , Banasik Karina , Brumpton Ben , Zhou Wei , Oddsson Asmundur , Tragante Vinicius , Hjorleifsson Kristjan E , Davidsson Olafur B , Rajamani Sridharan , Jonsson Stefan , Torfason Bjarni , Valgardsson Atli S , Thorgeirsson Gudmundur , Frigge Michael L , Thorleifsson Gudmar , Norddahl Gudmundur L , Helgadottir Anna , Gretarsdottir Solveig , Sulem Patrick , Jonsdottir Ingileif , Willer Cristen J , Hveem Kristian , Bundgaard Henning , Ullum Henrik , Arnar David O , Thorsteinsdottir Unnur , Gudbjartsson Daniel F , Holm Hilma , Stefansson Kari ,   DBDS Genomic Consortium, Andersen Steffen , Erikstrup Christian , Hansen Thomas F , Hjalgrim Henrik , Jemec Gregor , Jennum Poul , Nyegaard Mette , Bruun Mie T , Petersen Mikkel , Werge Thomas , Johansson Per I 
Published: January 2021

Abstract

Aims
The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.

Methods and results
We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10−20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P &gt; 0.05).

Conclusion
We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
Temporal changes in total and hippocampal brain volume and cognitive function in patients with chronic heart failure—the COGNITION.MATTERS-HF cohort study
Authors: Frey Anna , Homola György A , Henneges Carsten , Mühlbauer Larissa , Sell Roxane , Kraft Peter , Franke Maximilian , Morbach Caroline , Vogt Marius , Müllges Wolfgang , Ertl Georg , Solymosi László , Pirpamer Lukas , Schmidt Reinhold , Pham Mirko , Störk Stefan , Stoll Guido 
Published: January 2021

Abstract

Aims
We quantified the concurring dynamics affecting total and hippocampal brain volume and cognitive function in patients with chronic heart failure (HF) over a period of three years.

Methods and results
A total of 148 patients with mild stable HF entered this monocentric prospective cohort study: mean age 64.5 (10.8) years; 16.2% female; 77% in New York Heart Association functional classes I–II; 128 and 105 patients attended follow-up visits after 1 and 3 years, respectively. The assessment included cardiological, neurological, psychological work-up, and brain magnetic resonance imaging. Total and regional brain volumes were quantified using an operator-independent fully automated approach and reported normalized to the mean estimated intracranial volume. At baseline, the mean hippocampal volume was ∼13% lower than expected. However, the 3-year progressive hippocampal volume loss was small: −62 mm3 [95% confidence interval (CI) −81 to −42, P &lt; 0.0001). This corresponded to a relative change of −1.8% (95% CI −2.3 to −1.2), which was similar in magnitude as observed with physiological aging. Moreover, the load of white matter hypointensities increased within the limits of normal aging. Cognitive function during the 3-year observation period remained stable, with ‘intensity of attention’ as the only domain declining (LSmean −1.82 points, 95% CI −3.05 to −0.58, P = 0.004). After 3 years, performance in all domains of cognition remained associated with hippocampal volume (r ≥ 0.29).

Conclusion
In patients with predominantly mild HF, the markedly reduced hippocampal volume observed at baseline was associated with impaired cognitive function, but no accelerated deterioration in cognition and brain atrophy became evident over a mid-term period of three years.
Capturing the diversity of the human milk microbiota through culture-enriched molecular profiling: a feasibility study
Authors: Moossavi Shirin , Fontes Michelle E , Rossi Laura , Fusch Gerhard , Surette Michael G , Azad Meghan B 
Published: January 2021

ABSTRACTPrevious human milk studies have confirmed the existence of a highly diverse bacterial community using culture-independent and targeted culture-dependent techniques. However, culture-enriched molecular profiling of milk microbiota has not been done. Additionally, the impact of storage conditions and milk fractionation on microbiota composition is not understood. In this feasibility study, we optimized and applied culture-enriched molecular profiling to study culturable milk microbiota in eight milk samples collected from mothers of infants admitted to a neonatal intensive care unit. Fresh samples were immediately plated or stored at −80°C for 2 weeks (short-term frozen). Long-term samples were stored at −20°C for &gt;6 months. Samples were cultured using 10 different culture media and incubated both aerobically and anaerobically. We successfully isolated major milk bacteria, including Streptococcus, Staphylococcus and Bifidobacterium, from fresh milk samples, but were unable to culture any bacteria from the long-term frozen samples. Short-term freezing shifted the composition of viable milk bacteria from the original composition in fresh samples. Nevertheless, the inter-individual variability of milk microbiota composition was observed even after short-term storage. There was no major difference in the overall milk microbiota composition between milk fractions in this feasibility study. This is among the first studies on culture-enriched molecular profiling of the milk microbiota demonstrating the effect of storage and fractionation on milk microbiota composition.
THE GENETIC STRUCTURE OF NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER. XV. NATURE OF DEVELOPMENTAL HOMEOSTASIS FOR VIABILITY
Authors: Mukai Terumi , Chigusa Sadao I , Kusakabe Shin-Ichi 
Published: January 2021

ABSTRACT
Developmental homeostasis of relative viability was examined for homozygotes and heterozygotes using second chromosomes from two populations of Drosophila melanogaster. One was a chromosome population in which spontaneous mutations were allowed to accumulate since it was begun with a single near-normal second chromosome. The second was a natural population approximately at equilibrium. For the estimation of relative viability, the Cy method was employed (Wallace 1956), and environmental variance between simultaneously replicated cultures was used as the index of developmental homeostasis. A new method was used in the estimation of sampling variance for relative viability that was employed for the calculation of environmental variance (error variance between simultaneously replicated cultures — sampling variance). The following findings were obtained.: (1) The difference in environmental variance between homozygotes and heterozygotes could not be seen when a chromosome population with variation due to new mutations was tested. (2) When a chromosome group isolated from an approximate equilibrium population was examined, heterozygotes manifested a smaller environmental variance than the homozygotes if their relative viabilities were approximately the same. (3) There was a slight negative correlation between viability and environmental variance, although opposite results were found when the viabilities of individuals were high, especially when overdominance (coupling overdominance, Mukai 1969 a, b) was manifest. On the basis of these findings, it was concluded that developmental homeostasis was a product of natural selection, and its mechanism was discussed.
GENETIC VARIABILITY FOR DENSITY SENSITIVITY OF THREE COMPONENTS OF FITNESS IN DROSOPHILA MELANOGASTER
Authors: Marks R William 
Published: January 2021

ABSTRACT
This study examines natural genetic variation in density sensitivity of three components of fitness in Drosophila melanogaster using the method of chromosome extraction. Different lines are differentially sensitive to density. The distribution of measures of density sensitivity of chromosomal homozygotes is different from that of random chromosomal heterozygotes for both location and dispersion. Density sensitivity of the components is about as variable as any of the fitness components themselves at fixed densities. The consequences of the exact nature of this density dependence are discussed with respect to the stage of the life cycle at which density dependence occurs, and the mathematical form that it takes. There is no evidence of trade-offs among the components or their density sensitivity.
A STUDY OF rDNA MAGNIFICATION PHENOMENON IN A REPAIR-RECOMBINATION DEFICIENT MUTANT OF DROSOPHILA MELANOGASTER
Authors: Polito Lino C , Cavaliere Daniela , Zazo Anna , Furia Maria 
Published: January 2021

ABSTRACT
The rDNA magnification process consists of a rapid and inheritable rDNA increase occurring in bobbed males: in a few generations the bb loci acquire the wild-type rDNA value and reach a bb+ phenotype.—We have analyzed the rDNA magnification process in the repair-recombination-deficient mutant mei9a, both at the phenotypical and rDNA content levels. In mei9a bb double mutants the recovery of bb+ phenotype is strongly disturbed and the rDNA redundancy value fails to reach the wild-type level. The strong effect of this meiotic mutation on rDNA magnification suggests a close relationship between this phenomenon and the repair-recombination processes.
FILICIDAL RING-Y CHROMOSOMES IN D. MELANOGASTER
Authors: Stone James C 
Published: January 2021

ABSTRACT
Ring-Y chromosomes are recovered infrequently from crosses of ring-Y-bearing males to females of certain strains (Oster 1964). Experiments described here have unveiled a diverse class of genes that exert a maternal effect on the behavior during cleavage of these "filicidal" ring chromosomes. Cytological observations of inviable embryos have revealed that the ring-Y chromosome causes gross disorganization of the cleavage nuclei. This inviability may be equivalent to the "dominant lethality" attributed to unstable ring-X chromosomes (Hinton 1955; Pasztor 1971). Mapping studies indicate that no single region of the normal Y is solely responsible for the unusual behavior of ring-Y chromosomes.
CHI-STIMULATED RECOMBINATION BETWEEN PHAGE Λ AND THE PLASMID Λdv
Authors: Stahl Franklin W , Stahl Mary M , Young Lisa , Kobayashi Ichizo 
Published: January 2021

ABSTRACT
Chi promotes Rec-mediated recombination between phage λ DNA and the homologous plasmid λdv. In the absence of Chi, some of the interactions splice λdv into λ, whereas others patch information from λdv into λ. When Chi is in the phage DNA, splices and patches are increased in frequency by the same factor. This result strengthens the analogy between Chi and recombination-promoting elements in fungi. It also rules out one model for the previously reported orientation dependence of Chi phenotype.
CIS-TRANS EFFECTS INDUCED BY LINKAGE DISEQUILIBRIUM
Authors: Turelli Michael 
Published: January 2021

ABSTRACT
This note concerns theoretical and experimental studies of multifactorial traits, especially fitness and its components, in which (1) the loci studied are only a subset of those relevant to the character of interest and (2) the genotypes at the loci studied are in nonrandom association (linkage disequilibrium) with genotypes at the loci ignored. In these cases, phenotypic differences between cis and trans double heterozygotes can occur even though no linkage phase effects are inherent in the genetic determination of the trait. Examples are drawn from both theoretical and experimental work, and implications in both areas are discussed.
FREQUENCY OF γ-RAY INDUCED SPECIFIC LOCUS AND RECESSIVE LETHAL MUTATIONS IN MATURE GERM CELLS OF THE ZEBRAFISH, BRACHYDANIO RERIO
Authors: Chakrabarti Sankar , Streisinger George , Singer Fred , Walker Charline 
Published: January 2021

ABSTRACT
Specific locus and recessive lethal mutations are induced by γ-rays with approximately first order kinetics in the zebrafish (Brachydanio rerio) with frequencies of 4 × 10-5 r-1 and 4 × 10-3 r-1, respectively. The surprisingly low ratio (100:1) of recessive lethals to specific locus mutations may be due to the induction of large deficiencies by γ-rays.
ANALYSIS OF Y-LINKED MUTATIONS TO MALE STERILITY IN DROSOPHILA MELANOGASTER
Authors: Kennison James A 
Published: January 2021

ABSTRACT
The frequencies of newly induced male-sterilizing lesions on both the X and Y chromosomes of Drosophila melanogaster were determined after either 4000 r of γ-irradiation or adult feeding of ethyl methanesulfonate. The Y chromosome is approximately twice as sensitive as the X chromosome to newly induced male-sterilizing lesions after γ-irradiation, but slightly less sensitive after ethyl methanesulfonate treatment. A large proportion of the radiation-induced lesions are associated with Y-autosome or X-autosome translocations, with the Y chromosome recovered in translocations far in excess of the frequency expected from metaphase lengths. Although translocations between the X and Y chromosomes or between autosomes do not appear to sterilize heterozygous males, interchanges between sex chromosomes and autosomes often sterilize males carrying them in a dominant manner, suggesting that the organization of the genome is critical for normal spermatogenesis. Complementation tests between recessive Y-linked male-sterilizing mutants do not reveal the existence of any additional fertility loci beyond the six previously defined.
MOUSE MUTANT DEFICIENT IN d-AMINO ACID OXIDASE ACTIVITY
Authors: Konno Ryuichi , Yasumura Yosihiro 
Published: January 2021

ABSTRACT
d-Amino acid oxidase activity in the kidney homogenates of mice of seven strains was measured to search for a mutant for this enzyme. There was a consistent sex difference in the enzyme activity in these strains: male mice showed higher levels of the enzyme activity than females. In contrast to other strains, some mice of the ddY strain did not possess enzyme activity. This trait was inheritable, and a mouse stock without enzyme activity (DAO-) was established. The allele (Dao-1c) carried by the DAO- mice was recessive and behaved as a single autosomal gene in inheritance. Heterozygous mice for this gene (Dao-1 +/Dao-1c) showed nearly half the enzyme activity of the wild-type homozygotes (Dao-1 +/Dao-1 +), suggesting that Dao-1c is a null allele and that there is a gene dosage effect on the enzyme activity.
HUMAN MITOCHONDRIAL DNA VARIATION AND EVOLUTION: ANALYSIS OF NUCLEOTIDE SEQUENCES FROM SEVEN INDIVIDUALS
Authors: Aquadro Charles F , Greenberg Barry D 
Published: January 2021

ABSTRACT
We have analyzed nucleotide sequence variation in an approximately 900-base pair region of the human mitochondrial DNA molecule encompassing the heavy strand origin of replication and the D-loop. Our analysis has focused on nucleotide sequences available from seven humans. Average nucleotide diversity among the sequences is 1.7%, several-fold higher than estimates from restriction endonuclease site variation in mtDNA from these individuals and previously reported for other humans. This disparity is consistent with the rapidly evolving nature of this noncoding region. However, several instances of convergent or parallel gain and loss of restriction sites due to multiple substitutions were observed. In addition, other results suggest that restriction site (as well as pairwise sequence) comparisons may underestimate the total number of substitutions that have occurred since the divergence of two mtDNA sequences from a common ancestral sequence, even at low levels of divergence. This emphasizes the importance of recognizing the large standard errors associated with estimates of sequence variability, particularly when constructing phylogenies among closely related sequences. Analysis of the observed number and direction of substitutions revealed several significant biases, most notably a strand dependence of substitution type and a 32-fold bias favoring transitions over transversions. The results also revealed a significantly nonrandom distribution of nucleotide substitutions and sequence length variation. Significantly more multiple substitutions were observed than expected for these closely related sequences under the assumption of uniform rates of substitution. The bias for transitions has resulted in predominantly convergent or parallel changes among the observed multiple substitutions. There is no convincing evidence that recombination has contributed to the mtDNA sequence diversity we have observed.
THE EFFECT OF DDT ON THE POLYMORPHISM AT THE G6pd AND Pgd LOCI IN DROSOPHILA MELANOGASTER
Authors: Bijlsma R , Kerver J W M 
Published: January 2021

ABSTRACT
For the degradation of DDT and other chlorohydrocarbon insecticides energy in the form of NADPH is needed which for the greater part is supplied by the pentose phosphate shunt. Therefore the influence of DDT on the polymorphism at the G6pd and Pgd loci in Drosophila melanogaster was investigated by studying its effect on egg to adult survival and adult survival. The results show the existence of significant differences in fitness between the different genotypes of the two loci for both components. It is found that the effect of DDT supplementation differs significantly from the effect of sodium octanoate addition. DDT treatment also increases the activity of the pentose phosphate shunt as measured by the activity of G6PD and 6PGD. In larvae a 50% increase in activity is found and in adults a 100% increase. As there is little doubt that the activities of G6PD and 6PGD are somehow correlated with the fitness of flies, the data are discussed in relation to the in vitro and in vivo differences in activity between the different allozymes of both G6PD and 6PGD.
AN APPROACH TO POPULATION AND EVOLUTIONARY GENETIC THEORY FOR GENES IN MITOCHONDRIA AND CHLOROPLASTS, AND SOME RESULTS
Authors: Birky C William , Maruyama Takeo , Fuerst Paul 
Published: January 2021

ABSTRACT
We developed population genetic theory for organelle genes, using an infinite alleles model appropriate for molecular genetic data, and considering the effects of mutation and random drift on the frequencies of selectively neutral alleles. The effects of maternal inheritance and vegetative segregation of organelle genes are dealt with by defining new effective gene numbers, and substituting these for 2Ne in classical theory of nuclear genes for diploid organisms. We define three different effective gene numbers. The most general is N λ, defined as a function of population size, number of organelle genomes per cell, and proportions of genes contributed by male and female gametes to the zygote. In many organisms, vegetative segregation of organelle genomes and intracellular random drift of organelle gene frequencies combine to produce a predominance of homoplasmic cells within individuals in the population. Then, the effective number of organelle genes is Neo, a simple function of the numbers of males and females and of the maternal and paternal contributions to the zygote. Finally, when the paternal contribution is very small, Neo is closely approximated by the number of females, Nf. Then if the sex ratio is 1, the mean time to fixation or loss of new mutations is approximately two times longer for nuclear genes than for organelle genes, and gene diversity is approximately four times greater. The difference between nuclear and organelle genes disappears or is reversed in animals in which males have large harems. The differences between nuclear and organelle gene behavior caused by maternal inheritance and vegetative segregation are generally small and may be overshadowed by differences in mutation rates to neutral alleles. For monoecious organisms, the effective number of organelle genes is approximately equal to the total population size N. We also show that a population can be effectively subdivided for organelle genes at migration rates which result in panmixis for nuclear genes, especially if males migrate more than females.
EXPECTED LINKAGE DISEQUILIBRIUM FOR A NEUTRAL LOCUS LINKED TO A CHROMOSOMAL ARRANGEMENT
Authors: Strobeck Curtis 
Published: January 2021

ABSTRACT
The expected value of the squared linkage disequilibrium is derived for a neutral locus associated with a chromosomal arrangement that is maintained in the population by strong balancing selection. For a given value of recombination, the expected squared linkage disequilibrium is shown to decrease as the intensity of selection maintaining the arrangement increases. The transient behavior of the expected square linkage disequilibrium is also derived. This theory applies to loci that are closely linked to inversions in Drosophila species and to loci closely linked to the differential segments of the translocation complexes in ring-forming species of Oenothera. In both cases the strong linkage disequilibria that have been observed in natural populations can be explained by random drift.
MULTIPLE-LOCUS DEPARTURES FROM PANMICTIC EQUILIBRIUM WITHIN AND BETWEEN VILLAGE GENE POOLS OF AMERINDIAN TRIBES AT DIFFERENT STAGES OF AGGLOMERATION
Authors: Smouse Peter E , Neel James V , Liu Wanda 
Published: January 2021

ABSTRACT
A comparative analysis of departures from multiple-locus Hardy-Weinberg equilibrium is presented for a set of four tribal Indian groups (the Yanomama, Makiritare, Wapishana and Ticuna) from the lowlands of South America. These tribes span a range of agglomeration and acculturation from the most traditional, swidden horticulturalists to frontier townspeople. The small-group social organization typical of traditional horticulturalists leads to substantial departures from tribal panmixia, as manifested by the distribution of multiple-locus genotypes both within and between villages. Within villages, the departures from single-locus Hardy-Weinberg equilibrium are small and nonsignificant, but the departures from gametic equilibrium (independence of loci) are substantial, even for the unlinked loci we have used to characterize these populations. The departures from single-locus homogeneity across villages are also substantial. One of the normal concomitants of increasing acculturation in this setting is an increase in agglomeration. As agglomeration increases, the departures from multiple-locus panmixia decrease, a process that can be very rapid. We discuss both the shifting balance theory of evolution and punctuated evolutionary rates in light of the small group social organization that must have obtained throughout most of human evolution.