| 1. |
- Helsmoortel, Celine, et al.
(author)
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A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:4, s. 380-
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Journal article (peer-reviewed)abstract
- Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities(1), a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile- X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in nextgeneration sequencing, for the large majority of cases no molecular diagnosis can be established(2-7). Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/ SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD- associated genes known to date.
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| 2. |
- Robinson-Cohen, Cassianne, et al.
(author)
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Genetic Variants Associated with Circulating Fibroblast Growth Factor 23
- 2018
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In: Journal of the American Society of Nephrology. - : AMER SOC NEPHROLOGY. - 1046-6673 .- 1533-3450. ; 29:10, s. 2583-2592
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Journal article (peer-reviewed)abstract
- Background: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.Methods: We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m(2) to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.Results: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0x10(-24)), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.Conclusions: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.
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| 5. |
- Landegren, U., et al.
(author)
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Detecting genes with ligases.
- 1996
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In: Methods: a companion to Methods in Enzymology.. ; , s. 84-
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Book chapter (other academic/artistic)
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| 6. |
- Malmgren, H., et al.
(author)
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Rapid detection of a mutation hot-spot in the human androgen receptor
- 1996
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In: Clinical Genetics. - 0009-9163 .- 1399-0004. ; 50:4, s. 202-205
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Journal article (peer-reviewed)abstract
- Mutations of the human androgen receptor gene may disturb sexual development in males, and are inherited as an X-linked recessive trait. The vast majority of the mutations are familial. We have identified a large kindred with complete androgen insensitivity syndrome (CAIS) without detectable androgen-binding in genital skin fibroblasts. A single nucleotide substitution (C-to-T transition) was identified, resulting in an Arg855 to Cys in the androgen binding domain. To date, four independent CAIS families have been reported with this specific mutation that coincides with the propensity of cytosines at CpG dinucleotides to methylate. An allele-specific oligo-nucleotide assay was developed that allowed for the rapid and specific identification of this mutation hot-spot in individuals with androgen receptor insensitivity syndromes.
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| 7. |
- Milne, Richard, et al.
(author)
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Demonstrating trustworthiness when collecting and sharing genomic data : public views across 22 countries
- 2021
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In: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X .- 1756-994X. ; 13:1
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Journal article (peer-reviewed)abstract
- BackgroundPublic trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they are trustworthy. However, it is unclear what measures are most likely to demonstrate this.MethodsWe analyse the ‘Your DNA, Your Say’ online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.ResultsProviding transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data—endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.ConclusionsOur findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
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| 8. |
- Milne, Richard, et al.
(author)
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Return of genomic results does not motivate intent to participate in research for all: Perspectives across 22 countries
- 2022
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In: Genetics in Medicine. - : Elsevier BV. - 1098-3600 .- 1530-0366. ; 24:5, s. 1120-1129
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Journal article (peer-reviewed)abstract
- Purpose: The aim of this study was to determine how attitudes toward the return of genomic research results vary internationally. Methods: We analyzed the “Your DNA, Your Say” online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle-, and high-income countries, and these were gathered in 15 languages. We analyzed how participants responded when asked whether return of results (RoR) would motivate their decision to donate DNA or health data. We examined variation across the study countries and compared the responses of participants from other countries with those from the United States, which has been the subject of the majority of research on return of genomic results to date. Results: There was substantial variation in the extent to which respondents reported being influenced by RoR. However, only respondents from Russia were more influenced than those from the United States, and respondents from 20 countries had lower odds of being partially or wholly influenced than those from the United States. Conclusion: There is substantial international variation in the extent to which the RoR may motivate people's intent to donate DNA or health data. The United States may not be a clear indicator of global attitudes. Participants’ preferences for return of genomic results globally should be considered.
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