Human Genetics

http://link.springer.com/journal/439

List of Papers (Total 362)

Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus

Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Whole-genome sequencing of DNA samples from 71 Swedish patients...

Translating cancer genomics into precision medicine with artificial intelligence: applications, challenges and future perspectives

In the field of cancer genomics, the broad availability of genetic information offered by next-generation sequencing technologies and rapid growth in biomedical publication has led to the advent of the big-data era. Integration of artificial intelligence (AI) approaches such as machine learning, deep learning, and natural language processing (NLP) to tackle the challenges of...

De novo and inherited loss-of-function variants of ATP2B2 are associated with rapidly progressive hearing impairment

ATP2B2 encodes the PMCA2 Ca2+ pump that plays an important role in maintaining ion homeostasis in hair cells among others by extrusion of Ca2+ from the stereocilia to the endolymph. Several mouse models have been described for this gene; mice heterozygous for loss-of-function defects display a rapidly progressive high-frequency hearing impairment. Up to now ATP2B2 has only been...

The impact of GJA8 SNPs on susceptibility to age-related cataract

The gap junction protein alpha 8 (GJA8) gene has been widely studied in human congenital cataracts. However, little is known about its relationship with age-related cataract (ARC). In this study, three GJA8-tagged single nucleotide polymorphisms related to an increased ARC risk were identified: rs2132397 for general ARC under both dominant and additive models; rs7541950 for...

Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci

Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association...

De novo unbalanced translocations have a complex history/aetiology

We investigated 52 cases of de novo unbalanced translocations, consisting in a terminally deleted or inverted-duplicated deleted (inv-dup del) 46th chromosome to which the distal portion of another chromosome or its opposite end was transposed. Array CGH, whole-genome sequencing, qPCR, FISH, and trio genotyping were applied. A biparental origin of the deletion and duplication was...

The genetic architecture of aniridia and Gillespie syndrome

Absence of part or all of the iris, aniridia, is a feature of several genetically distinct conditions. This review focuses on iris development and then the clinical features and molecular genetics of these iris malformations. Classical aniridia, a panocular eye malformation including foveal hypoplasia, is the archetypal phenotype associated with heterozygous PAX6 loss-of-function...

South Korea: in the midst of a privacy reform centered on data sharing

With rapid developments in genomic and digital technologies, genomic data sharing has become a key issue for the achievement of precision medicine in South Korea. The legal and administrative framework for data sharing and protection in this country is currently under intense scrutiny from national and international stakeholders. Policymakers are assessing the relevance of...

Germany: a fair balance between scientific freedom and data subjects’ rights?

With the German Bundestag’s adoption of the Data Protection Adaptation and Implementation Act EU (DSAnpUG-EU) on 30 June 2017, the adaptation of German law to the General Data Protection Regulation (GDPR) has begun (Gesetz zur Anpassung des Datenschutzrechts an die Verordnung (EU) 2016/679 und zur Umsetzung der Richtlinie (EU) 2016/680 (Datenschutz-Anpassungs- und...

United Kingdom: transfers of genomic data to third countries

In the United Kingdom (UK), transfer of genomic data to third countries is regulated by data protection legislation. This is a composite of domestic and European Union (EU) law, with EU law to be adopted as domestic law when Brexit takes place. In this paper we consider the content of data protection legislation and the likely impact of Brexit on transfers of genomic data from...

The hedgehog pathway and ocular developmental anomalies

Mutations in effectors of the hedgehog signaling pathway are responsible for a wide variety of ocular developmental anomalies. These range from massive malformations of the brain and ocular primordia, not always compatible with postnatal life, to subtle but damaging functional effects on specific eye components. This review will concentrate on the effects and effectors of the...

United States: law and policy concerning transfer of genomic data to third countries

This paper provides an overview of US laws and related guidance documents affecting transfer of genomic data to third countries, addressing the domains of consent, privacy, security, compatible processing/adequacy, and oversight. In general, US laws governing research and disclosure and use of data generated within the health care system do not impose different requirements on...

International data-sharing norms: from the OECD to the General Data Protection Regulation (GDPR)

The evolution of genomic research and its integration into clinical practice, as they become international—even global—endeavors, has brought us to a place where scientists and clinicians may now only ignore the rules governing international data sharing at their own peril. Open data policies, on the one hand, increasingly require custodians of others’ genomic data to make it as...

China: concurring regulation of cross-border genomic data sharing for statist control and individual protection

This paper reviews the major legal instruments and self-regulations that bear heavily on the cross-border sharing of genomic data in China. It first maps out three overlapping frameworks on genomic data and analyzes their underpinning policy goals. Subsequent sections examine the regulatory approaches with respect to five aspects of responsible use and sharing of genomic data...

Integrated analysis of human genetic association study and mouse transcriptome suggests LBH and SHF genes as novel susceptible genes for amyloid-β accumulation in Alzheimer’s disease

Alzheimer’s disease (AD) is a common neurological disease that causes dementia in humans. Although the reports of associated pathological genes have been increasing, the molecular mechanism leading to the accumulation of amyloid-β (Aβ) in human brain is still not well understood. To identify novel genes that cause accumulation of Aβ in AD patients, we conducted an integrative...

Evidence of distinct RELN and TGFB1 genetic associations in familial and non-familial otosclerosis in a British population

Otosclerosis is a common form of hearing loss which typically presents in young adults. The disease has a familial, monogenic form and a non-familial form with a more complex aetiology. A previous genome wide association study identified evidence that variants within RELN are associated with the condition. Other genes in which an association has been reported include BMP2, COL1A1...

Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease

Single nucleotide variants (SNVs) within and surrounding the complement receptor 1 (CR1) gene show some of the strongest genome-wide association signals with late-onset Alzheimer’s disease. Some studies have suggested that this association signal is due to a duplication allele (CR1-B) of a low copy repeat (LCR) within the CR1 gene, which increases the number of complement C3b/C4b...

Genomic trade-offs: are autism and schizophrenia the steep price of the human brain?

Evolution often deals in genomic trade-offs: changes in the genome that are beneficial overall persist even though they also produce disease in a subset of individuals. Here, we explore the possibility that such trade-offs have occurred as part of the evolution of the human brain. Specifically, we provide support for the possibility that the same key genes that have been major...