Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 14 de 14
Filter
1.
Nature ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843826

ABSTRACT

Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and their widespread integration as a means of transport remains contentious2-4. Here we assemble a collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged around 2200 BCE, through close-kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than approximately 2700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe around 3000 BCE and earlier3,5. Finally, we detect significantly shortened generation times at Botai around 3500 BCE, a settlement from central Asia associated with corrals and a subsistence economy centred on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines.

3.
Genome Med ; 13(1): 90, 2021 05 21.
Article in English | MEDLINE | ID: mdl-34020708

ABSTRACT

BACKGROUND: We aimed to define the clinical and variant spectrum and to provide novel molecular insights into the DHX30-associated neurodevelopmental disorder. METHODS: Clinical and genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, and our network of collaborators. We investigated the impact of novel missense variants with respect to ATPase and helicase activity, stress granule (SG) formation, global translation, and their effect on embryonic development in zebrafish. SG formation was additionally analyzed in CRISPR/Cas9-mediated DHX30-deficient HEK293T and zebrafish models, along with in vivo behavioral assays. RESULTS: We identified 25 previously unreported individuals, ten of whom carry novel variants, two of which are recurrent, and provide evidence of gonadal mosaicism in one family. All 19 individuals harboring heterozygous missense variants within helicase core motifs (HCMs) have global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities. These variants impair the ATPase and helicase activity of DHX30, trigger SG formation, interfere with global translation, and cause developmental defects in a zebrafish model. Notably, 4 individuals harboring heterozygous variants resulting either in haploinsufficiency or truncated proteins presented with a milder clinical course, similar to an individual harboring a de novo mosaic HCM missense variant. Functionally, we established DHX30 as an ATP-dependent RNA helicase and as an evolutionary conserved factor in SG assembly. Based on the clinical course, the variant location, and type we establish two distinct clinical subtypes. DHX30 loss-of-function variants cause a milder phenotype whereas a severe phenotype is caused by HCM missense variants that, in addition to the loss of ATPase and helicase activity, lead to a detrimental gain-of-function with respect to SG formation. Behavioral characterization of dhx30-deficient zebrafish revealed altered sleep-wake activity and social interaction, partially resembling the human phenotype. CONCLUSIONS: Our study highlights the usefulness of social media to define novel Mendelian disorders and exemplifies how functional analyses accompanied by clinical and genetic findings can define clinically distinct subtypes for ultra-rare disorders. Such approaches require close interdisciplinary collaboration between families/legal representatives of the affected individuals, clinicians, molecular genetics diagnostic laboratories, and research laboratories.


Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/genetics , RNA Helicases/genetics , Animals , Biomarkers , Gene Expression , Gene Knockdown Techniques , Genetic Association Studies/methods , Germ-Line Mutation , HEK293 Cells , Humans , Immunohistochemistry , Mutation , Phenotype , RNA Helicases/chemistry , RNA Helicases/metabolism , Zebrafish
4.
Genes (Basel) ; 11(12)2020 12 18.
Article in English | MEDLINE | ID: mdl-33353040

ABSTRACT

Warmblood fragile foal syndrome (WFFS) is an autosomal recessive disorder caused by a single nucleotide variant in the procollagen-lysine-2-oxoglutarate-5-dioxygenase 1 gene (PLOD1:c.2032G>A, p.Gly678Arg). Homozygosity for the PLOD1 variant causes an Ehler-Danlos-like syndrome, which has to date only been reported in warmblood breeds but the WFFS allele has been also detected in the Thoroughbred. To investigate the breed distribution of the WFFS allele, 4081 horses belonging to 38 different breeds were screened. In total, 4.9% of the horses representing 21 breeds carried the WFFS allele. The affected breeds were mainly warmbloods, with carrier frequency as high as 17% in the Hanoverian and Danish Warmblood. The WFFS allele was not detected in most non-warmblood breeds. Exceptions include WFFS carriers in the Thoroughbred (17/716), Haflinger (2/48), American Sport Pony (1/12), and Knabstrupper (3/46). The origin of the WFFS allele remains unknown. The Arabian breed and specifically the stallion Bairactar Or. Ar. (1813), whose offspring were reported to have a similar phenotype in the 19th century, were hypothesized as the origin. DNA from a museum sample of Bairactar Or. Ar. showed that he did not carry the mutated allele. This result, together with the genotypes of 302 Arabians, all homozygous for the reference allele, does not support an Arabian origin of the WFFS allele. Our extensive survey shows the WFFS allele to be of moderate frequency and concern in warmbloods and also in breeds where it may not be expected.


Subject(s)
Horse Diseases/genetics , Horses/genetics , Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase/genetics , Skin Diseases, Genetic/veterinary , Alleles , Animals , Breeding , Datasets as Topic , Europe/epidemiology , Horse Diseases/epidemiology , Horses/classification , Mutation, Missense , Point Mutation , Skin Diseases, Genetic/epidemiology , Skin Diseases, Genetic/genetics , Species Specificity , United States/epidemiology
5.
J Equine Vet Sci ; 88: 102950, 2020 05.
Article in English | MEDLINE | ID: mdl-32303326

ABSTRACT

The roan coat color in horses is characterized by dispersed white hair and dark points. This phenotype segregates in a broad range of horse breeds, while the underlying genetic background is still unknown. Previous studies mapped the roan locus to the KIT gene on equine chromosome 3 (ECA3). However, this association could not be validated across different horse breeds. Performing a genome-wide association analysis (GWAS) in Noriker horses, we identified a single nucleotide polymorphism (SNP) (ECA3:g.79,543.439 A > G) in the intron 17 of the KIT gene. The G -allele of the top associated SNP was present in other roan horses, namely Quarter Horse, Murgese, Slovenian, and Belgian draught horse, while it was absent in a panel of 15 breeds, including 657 non-roan horses. In further 379 gray Lipizzan horses, eight animals exhibited a heterozygous genotype (A/G). Comparative whole-genome sequence analysis of the KIT region revealed two deletions in the downstream region (ECA3:79,533,217_79,533,224delTCGTCTTC; ECA3:79,533,282_79,533,285delTTCT) and a 3 bp deletion combined with 17 bp insertion in intron 20 of KIT (ECA3:79,588,128_79,588,130delinsTTATCTCTATAGTAGTT). Within the Noriker sample, these loci were in complete linkage disequilibrium (LD) with the identified top SNP. Based upon pedigree information and historical records, we were able to trace back the genetic origin of roan coat color to a baroque gene pool. Furthermore, our data suggest allelic heterogeneity and the existence of additional roan alleles in ponies and breeds related to the English Thoroughbred. In order to study the roan phenotype segregating in those breeds, further association and verification studies are required.


Subject(s)
Genome-Wide Association Study , Polymorphism, Single Nucleotide , Alleles , Animals , Genome-Wide Association Study/veterinary , Hair Color/genetics , Horses/genetics , Phenotype , Polymorphism, Single Nucleotide/genetics
6.
Mov Disord ; 32(11): 1594-1599, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28861893

ABSTRACT

BACKGROUND: Whether antidiabetic glitazone drugs protect against Parkinson's disease remains controversial. Although a single clinical trial showed no evidence of disease modulation, retrospective studies suggest that a disease-preventing effect may be plausible. The objective of this study was to examine if the use of glitazone drugs is associated with a lower incidence of PD among diabetic patients. METHODS: We compared the incidence of PD between individuals with diabetes who used glitazones, with or without metformin, and individuals using only metformin in the Norwegian Prescription Database. This database contains all prescription drugs dispensed for the entire Norwegian population. We identified 94,349 metformin users and 8396 glitazone users during a 10-year period and compared the incidence of PD in the 2 groups using Cox regression survival analysis, with glitazone exposure as a time-dependent covariate. RESULTS: Glitazone use was associated with a significantly lower incidence of PD compared with metformin-only use (hazard ratio, 0.72; 95% confidence interval, 0.55-0.94; P = 0.01). CONCLUSIONS: The use of glitazones is associated with a decreased risk of incident PD in populations with diabetes. Further studies are warranted to confirm and understand the role of glitazones in neurodegeneration. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Parkinson Disease/prevention & control , Thiazolidinediones/pharmacology , Adult , Aged , Aged, 80 and over , Databases, Factual/statistics & numerical data , Diabetes Mellitus, Type 2/epidemiology , Drug Prescriptions/statistics & numerical data , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Male , Middle Aged , Norway/epidemiology , Parkinson Disease/epidemiology
7.
Tidsskr Nor Laegeforen ; 137(9): 651, 2017 May.
Article in Norwegian | MEDLINE | ID: mdl-28468491
8.
Epilepsy Behav ; 62: 251-7, 2016 09.
Article in English | MEDLINE | ID: mdl-27513352

ABSTRACT

OBJECTIVE: The aim of this study was to investigate life satisfaction in women with epilepsy during and after pregnancy. METHODS: The study was based on the Norwegian Mother and Child Cohort Study, including 102,265 women with and without epilepsy from the general population. Investigation took place at pregnancy weeks 15-19 and 6 and 18months postpartum. Women with epilepsy were compared with a reference group without epilepsy. RESULTS: The proportion of women with epilepsy was 0.6-0.7% at all three time points. Women with epilepsy reported lower life satisfaction and self-esteem both during and after pregnancy compared with the references. Single parenting correlated negatively with life satisfaction in epilepsy during the whole study period. Epilepsy was associated with lower levels of relationship satisfaction and higher levels of work strain during pregnancy and lower levels of self-efficacy and satisfactory somatic health 18months postpartum. Adverse life events, such as divorce, were more common in women with epilepsy compared with the references, and fewer women with epilepsy had a paid job 18months postpartum. SIGNIFICANCE: Reduced life satisfaction associated with epilepsy during and after pregnancy showed that, even in a highly developed welfare society, women with epilepsy struggle. Mothers with epilepsy and their partners should be examined for emotional complaints and partnership satisfaction during and after pregnancy. Validated screening tools are available for such measures.


Subject(s)
Epilepsy/psychology , Mothers/psychology , Personal Satisfaction , Postpartum Period/psychology , Self Concept , Adult , Cohort Studies , Female , Humans , Norway , Parenting , Pregnancy , Self Efficacy , Young Adult
9.
PLoS One ; 10(12): e0144159, 2015.
Article in English | MEDLINE | ID: mdl-26637130

ABSTRACT

OBJECTIVES: To investigate psychiatric disorders, adverse social aspects and quality of life in men with epilepsy during partner's pregnancy. METHOD: We used data from the Norwegian Mother and Child Cohort Study, including 76,335 men with pregnant partners. Men with epilepsy were compared to men without epilepsy, and to men with non-neurological chronic diseases. RESULTS: Expecting fathers in 658 pregnancies (mean age 31.8 years) reported a history of epilepsy, 36.9% using antiepileptic drugs (AEDs) at the onset of pregnancy. Symptoms of anxiety or depression were increased in epilepsy (7.0% and 3.9%, respectively) vs. non-epilepsy (4.6% and 2.5%, respectively, p = 0.004 and 0.023), and so were new onset symptoms of depression (2.0% vs. 1.0%, p < 0.031) and anxiety (4.3% vs. 2.3%, p = 0.023). Low self-esteem (2.5%) and low satisfaction with life (1.7%) were more frequent among fathers with epilepsy compared to fathers without epilepsy (1.3% and 0.7%, respectively, p = 0.01 and 0.010). Adverse social aspects and life events were associated with epilepsy vs. both reference groups. Self-reported diagnoses of ADHD (2.2%) and bipolar disorder (1.8%) were more common in epilepsy vs. non-epilepsy (0.4% and 0.3%, respectively, p = 0.002 and 0.003) and non-neurological chronic disorders (0.5% and 0.5%, respectively, p = 0.004 and 0.018). A screening tool for ADHD symptoms revealed a higher rate compared to self-reported ADHD (9.5% vs. 2.2%, p < 0.001). CONCLUSION: Expecting fathers with epilepsy are at high risk of depression and anxiety, adverse socioeconomic aspects, low self-esteem, and low satisfaction with life. Focus on mental health in fathers with epilepsy during and after pregnancy is important. The use of screening tools can be particularly useful to identify those at risk.


Subject(s)
Epilepsy/psychology , Fathers/psychology , Mental Disorders/epidemiology , Quality of Life/psychology , Social Behavior Disorders/epidemiology , Adult , Anticonvulsants/therapeutic use , Comorbidity , Cross-Sectional Studies , Epilepsy/drug therapy , Female , Humans , Male , Mental Disorders/etiology , Norway , Pregnancy , Psychiatric Status Rating Scales , Self Report , Social Behavior Disorders/etiology
10.
Seizure ; 28: 81-4, 2015 May.
Article in English | MEDLINE | ID: mdl-25794467

ABSTRACT

PURPOSE: The aim was to investigate the prevalence of eating disorders and its relation to pregnancy and delivery complications in childbearing women with epilepsy (WWE). METHOD: This study is based on The Norwegian Mother and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway. Epilepsy was reported in 706 pregnancies. The remaining cohort (n=106,511) served as the reference group. Eating disorders were diagnosed using DSM-IV criteria adjusted for pregnancy. The risk of preeclampsia, gestational hypertension, diabetes and weight gain during pregnancy as well as delivery outcome (small for gestational age, large for gestational age, ponderal index, low APGAR score, small head circumference) were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for maternal age, smoking, parity and socioeconomic factors. RESULTS: Pregnant WWE were significantly more likely to have binge eating disorder (6.5% vs. 4.7%, p<0.05). WWE and comorbid eating disorders had significantly more preeclampsia (7.9% vs. 3.7%, p<0.05), peripartum depression and/or anxiety (40.4% vs. 17.8%, p<0.001) and operative delivery (38.2% vs. 23.5%, p<0.001) than the reference group without epilepsy or eating disorders. After adjustment for confounders, a significantly increased risk of operative delivery (OR 1.96, CI 1.26-3.05) and peripartum depression and/or anxiety (OR 2.17, CI 1.40-3.36) was demonstrated. CONCLUSION: Eating disorders in WWE contribute to the increased risk of pregnancy and delivery complications. Health personnel should be aware of eating disorders in WWE and refer them for treatment before pregnancy.


Subject(s)
Anticonvulsants/adverse effects , Epilepsy , Feeding and Eating Disorders/complications , Feeding and Eating Disorders/epidemiology , Pregnancy Complications/epidemiology , Chi-Square Distribution , Cohort Studies , Epilepsy/complications , Epilepsy/drug therapy , Epilepsy/epidemiology , Female , Humans , Logistic Models , Male , Norway , Pregnancy , Pregnant Women
11.
Epilepsia ; 56(1): 28-39, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25524160

ABSTRACT

OBJECTIVE: To assess incidence, prevalence, risk factors, and prognosis of peripartum depression and anxiety in a prospective study of women with epilepsy. METHOD: Pregnancies in women with epilepsy (n=706) were compared to pregnancies in all women without epilepsy (n=106,511) including women with specified nonepileptic chronic diseases (n=8,372) in the Norwegian Mother and Child Cohort Study. The database was linked to the Medical Birth Registry of Norway. Depression and anxiety were assessed with validated questionnaires five times from the second trimester to 36 months after delivery. Blood was drawn for analysis of antiepileptic drug (AED) concentrations. RESULTS: Women with epilepsy more often had peripartum depression (26.7%) or anxiety (22.4%) than women without epilepsy (18.9% and 14.8%, respectively, p<0.001 for both comparisons) and women with other chronic diseases (23.1% and 18.4%, respectively, p=0.03 and 0.01). Women using AEDs during pregnancy were especially at risk regardless of AED type. The risk further increased with the use of multiple AEDs and with high doses and/or plasma levels. Risk factors associated with peripartum depression and/or anxiety in the epilepsy cohort were high seizure frequency, a history of physical and/or sexual abuse, adverse socioeconomic factors, previous loss of a child, AED use, unplanned pregnancy, and prepregnancy depression and/or anxiety. The recovery rate 3 years after delivery was lower for women with epilepsy with a history of depression/anxiety or physical/sexual abuse than for women without epilepsy. Depressed women with epilepsy were less frequently treated with antidepressive drugs during pregnancy than women without epilepsy. SIGNIFICANCE: Women with epilepsy frequently have depression and anxiety during and after pregnancy. Patients at risk should be identified before delivery as depressive symptoms could be undertreated in this group.


Subject(s)
Anxiety/epidemiology , Depression, Postpartum/epidemiology , Depression/epidemiology , Depressive Disorder/epidemiology , Epilepsy/epidemiology , Pregnancy Complications/epidemiology , Adult , Anticonvulsants/therapeutic use , Antidepressive Agents/therapeutic use , Anxiety/psychology , Anxiety/therapy , Cohort Studies , Depression/psychology , Depression/therapy , Depression, Postpartum/psychology , Depression, Postpartum/therapy , Depressive Disorder/psychology , Depressive Disorder/therapy , Epilepsy/drug therapy , Epilepsy/psychology , Female , Humans , Incidence , Norway/epidemiology , Pregnancy , Pregnancy Complications/psychology , Pregnancy Complications/therapy , Prevalence , Prognosis , Prospective Studies , Risk Factors , Surveys and Questionnaires , Young Adult
12.
Epilepsy Behav ; 29(2): 379-85, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24074883

ABSTRACT

OBJECTIVE: The objective of this study was to investigate psychiatric disease and social aspects in young women with epilepsy before and during pregnancy. METHOD: The study included self-reported data from 106,935 pregnancies. RESULTS: Seven hundred eleven women reported having epilepsy, and 45.9% of them were using antiepileptic drugs (AEDs). Compared to the reference group, self-reported eating disorders and depression were increased in the untreated epilepsy group before pregnancy. Both AED-treated and untreated women with epilepsy reported higher depression scores as assessed by the Hopkins Symptom Checklist, and the Lifetime Major Depression scale was increased in AED-treated women. Antiepileptic drug treatment was linked to low income (27.4% vs. 18.4%, p<0.001) and no income (5.5% vs. 2.6%, p=0.001). Low educational level was associated with epilepsy in AED-treated and untreated women (50.5%, p<0.001 and 46.9%, p<0.001 vs. 32.2%), as was unemployment due to disability (7.9%, p<0.001 and 6.5%, p<0.001 vs. 1.5%) and single parenting (4.4%, p=0.016 and 4.5%, p=0.007 vs. 2.4%). No difference was found for smoking, alcohol use, or narcotic use. CONCLUSION: Symptoms of depression were associated with epilepsy both during and before pregnancy. Epilepsy was linked to eating disorders before pregnancy. Unemployment, single parenting, and low educational level were linked to epilepsy in young pregnant females. Efforts aiming at treatment and screening for psychiatric comorbidity in pregnant women with epilepsy are important in the follow-up of these patients.


Subject(s)
Epilepsy/epidemiology , Mental Disorders/epidemiology , Mental Disorders/etiology , Mother-Child Relations , Social Behavior Disorders/epidemiology , Social Behavior Disorders/etiology , Adult , Anticonvulsants/therapeutic use , Cohort Studies , Comorbidity , Epilepsy/drug therapy , Female , Humans , Male , Norway , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Complications/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Prenatal Exposure Delayed Effects/etiology , Psychiatric Status Rating Scales , Young Adult
13.
J Public Health (Oxf) ; 35(2): 278-85, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23292092

ABSTRACT

BACKGROUND: Mental health consequences related to divorce have been documented, but might be caused by concomitant factors such as conflicts and loss of parental contact (PC). We investigated these relationships and mental health among adolescents. METHODS: The study was based on data from four cross-sectional surveys carried out between 1997 and 2009 among tertiary school students in Førde, Norway. We established two groups according to divorce experience (DE) with or without loss of PC. Frequencies of DEs were calculated with 95% confidence intervals. The group with no DE was used as reference group in all the analyses. RESULTS: The divorce rate increased by 34% (6.8% absolute increase) between 1997 and 2009, but no sign of attenuated effects on emotional health was observed. Mental complaints were not attenuated as time since divorce increased. A majority of those losing contact with parents had no contact with their fathers. The study revealed only a modest increase of health complaints if PC was preserved, but a marked increase when the adolescents experienced loss of PC following the divorce. Interaction analyses showed no gender differences, and parental support and confidence in parent(s) did not mediate the associations between divorce and distress. CONCLUSIONS: Emotional distress after divorce is not attenuated as divorce prevalence increases, but the deleterious effects of divorce on the well-being of adolescents seem to be confined to those experiencing a concomitant loss of PC. Efforts aiming at reducing parental hostility and improving mutual parental responsibility and care therefore seem important.


Subject(s)
Divorce/psychology , Mental Health , Parent-Child Relations , Psychology, Adolescent , Adolescent , Cross-Sectional Studies , Divorce/trends , Female , Humans , Male , Norway , Parents
SELECTION OF CITATIONS
SEARCH DETAIL
...