bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disability: Western Theories
Authors: Woodin Sarah L 
Published: April 2013

Abstract

The theoretical underpinnings of conventional, individualistic medical conceptions of disability have in recent decades been challenged by various socio‐political approaches rooted in the collective experiences of disabled people and their organisations. Disability studies has developed both within and outside the academy primarily through an analysis of the structures and practices that marginalise disabled people in society. In recent decades theoretical approaches have become wider and among others these now encompass materialism, cultural studies, poststructuralism, feminism and phenomenology. Recent debates have centred on the body, the degree to which it should be a focus for social investigation and how it should be theorised. All of this has significant implications for proponents of genetic interventions as solutions to the problem of disability.

Key Concepts:

Individual, medical conceptions of disability have been challenged by socio‐political approaches.

Theoretical understandings of disablement have been given impetus by increasing evidence of social causes and implications.

Western theories of disability are characterised by increasing diversity of approaches, including materialist, cultural and poststructuralist.

Scientific understandings of disability have profound implications for life opportunities and situations of disabled people.
Disability, Human Rights and Contemporary Genetics
Authors: Scully Jackie Leach 
Published: April 2013

Abstract

In recent years, disabled people have been organised as a new social movement to promote their civil and human rights. At the same time, advances in genetic knowledge, especially the development of prenatal and preconception screening programmes, offer active selection against the birth of people with genetically based disability. Many disabled people are deeply concerned that selective genetic technologies bias the social context in which reproductive choices are made, implicitly questioning the right of disabled people to exist. However, it can be argued that bodily variation, even in the forms that lead to disability, should be acknowledged as part of the diversity of human embodiment. Steps in this direction can be seen in the language of human rights instruments such as the United Nations Convention on the Rights of Persons with Disabilities. Genetics can offer support for the idea that genotypic and phenotypic diversity is a natural and positive part of human societies.

Key Concepts:

During the last quarter of the twentieth century, disabled people began to be organised as a new social movement to promote their civil and human rights. As a result, many of the barriers to full participation of disabled people in society are beginning to be dismantled.

At the same time, advances in genetic knowledge have led to the growing use of technologies of genetic testing, in prenatal and preconception genetic screening programs as well as postnatal testing.

Genetics therefore holds out the promise of improving population health by reducing/eradicating genetically based disability, through selection against the birth of people with disabilities rather than through the amelioration or cure of genetic conditions.

The disability rights movement and genetics therefore represent two distinct ways of thinking about the biological meaning of disability.

Although many disabled people welcome medical and specifically genetic research, others have concerns about the way that the ready availability of genetic testing and screening changes the context in which reproductive decisions around disability are made.

Some people argue that bodily variation, even in the forms that lead to disability, should be acknowledged as part of the diversity of human embodiment.

Genetics offers some support for the idea that genotypic and phenotypic diversity is a natural part of biological populations and of human societies.

A number of recent legal instruments, including the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD), seek to protect the human rights of disabled people. Nevertheless, within the disability community there is concern that selective genetic technologies challenge the fundamental right of disabled people to exist.

Issues raised by the debate on variation and genetics will become increasingly important for nondisabled people as well, as the genetic factors that play a role in both normal variations and behaviours and common diseases are uncovered.
Twin Studies
Authors: Trumbetta Susan L 
Published: April 2013

Abstract

Twin studies provide useful tools for genetic and epigenetic research and also for studying the effects of nongenetic variables while controlling for genetic variation. Classic twin studies compare the phenotypic similarity of monozygotic to dizygotic twin pairs sampled from a population in order to estimate the relative influences of genetic and environmental factors on that phenotype in that population. Twin similarities may be of genetic or environmental origin; in twins reared apart, we see genetically influenced similarities emerge in very different environments. Phenotypically discordant monozygotic twins may reveal nonshared, nongenetic sources of influence on the development of that phenotype. Virtual twins, like adoptees, are biologically unrelated, and can teach us how children's rearing environments may either similarly or differentially affect their development, while holding age and cohort constant. Children‐of‐twins designs can help us detect gene‐correlated environments and distinguish between genetic and cultural factors in the transmission of complex phenotypes.

Key Concepts:

Twin studies can be used to explore a range of questions, from genetic variation in a trait in a population to the effects of specific epigenetic changes on gene expression to questions in evolutionary psychology.

Monozygotic (MZ) twins, also known as identical twins, typically share 100% of their genome and dizygotic (DZ) twins, also known as fraternal twins, share, on average, 50% of their genome. Classic twin studies use this information to estimate the relative proportions of genetic and environmental influence on a given phenotype in a given population.

Nonadditive genetic effects can make MZ twins more than twice as similar as DZ twins.

Effects of shared environments can make MZ twins less than twice as similar as DZ twins.

Studies of twins reared apart combine aspects of both twin study and adoption study designs. Remarkable similarities between MZ twins reared apart suggest a strong influence of genetic factors, and especially, of genes in specific combinations, on behavioural phenotypes.

Phenotypically discordant MZ twins may help researchers to isolate environmental and developmental contributors to, and results of, the development of that phenotype.

Phenotypically discordant MZ twins also help scientists to identify epigenetic changes that create within‐pair differences in gene expression and explain some of the within‐pair phenotypic differences.

Children‐of‐twins studies are useful in estimating the degree to which parental genotype is correlated with the offspring‐rearing environment (passive gene–environment correlation) and also in separating genetic transmission from environmental transmission (the effects of parental rearing environment).
Alzheimer Disease: Genetic and Environmental Influences
Authors: Reynolds Chandra A 
Published: April 2013

Abstract

Alzheimer disease (AD) is a complex, progressive neurodegenerative disease. Prevalence of AD is expected to grow substantially, although predictions may shift given future treatment interventions or higher levels of engagement in lifestyle delaying factors that may reduce risk. Several mutations have been characterised and susceptibility genes implicated as playing a role in the disorder. The apolipoprotein E (APOE) ε4 allele remains the best‐established susceptibility gene for late‐onset AD. Although a substantial proportion of the liability for AD may be accounted for by genetic factors, heterogeneity or differences in aetiology are important to consider. Environmental factors probably play a significant role, such as education, head injury and nonsteroidal anti‐inflammatory drugs (NSAIDs) use, as well as obesity, diabetes, physical activity and cognitively engaging leisure activities. The extent to which susceptibility genes interact with environmental factors may provide further clues to aetiology. Lastly, a developmental longitudinal perspective on the salience of particular risk and protective factors across the life course may illuminate etiologies and potential points of intervention.

Key Concepts:

The prevalence of Alzheimer disease (AD) will continue to rise globally, quadrupling by 2050.

The aetiology of AD is multifactorial.

Early‐onset Alzheimer disease (AD) is caused by rare mutations in three genes:
APP, PSEN1
and
PSEN2
.

Late‐onset AD is complex whereby the genetic contribution to the liability for AD may be as high as 79%.

The APOE ɛ4 allele increases the risk for late‐onset Alzheimer disease.

Genome‐wide gene association studies (GWAS) were instrumental in identifying new susceptibility genes for late‐onset AD beyond the
APOE
and
SORL1
candidates, including:
ABCA7
,
BIN1
,
CD33
,
CD2AP
,
CLU
,
CR1
,
EPHA1
,
MS4A4E/MS4A6A
and
PICALM
.

Risk and protective factors appear to play a role in AD risk, such as education, head injury, physical activity, cognitively engaging leisure activities and NSAIDs use.
Chromatin Structure and Domains
Authors: Grimaud Charlotte 
Published: April 2013

AbstractIn the cell nucleus,deoxyribonucleic acid(DNA) is associated with nuclear proteins called histones to form chromatin. According to the type of factors that bind it, chromatin is organised into different subdomains.Chromatin structure is essential to compact DNA but it is also crucial for the proper development of multicellular organisms. Indeed, it is a highly organised structure through which, genetic material is modulated to regulate nuclear processes, including transcription, replication and DNA repair. It is notably regulated via reversible covalent histone modifications. These multiple modifications deposited on chromatin by different histone modifying enzymes, serve as specific recognition signal for DNA‐regulating proteins. More recently, spatial organisation of chromosomes in the nucleus has been identified as a critical feature for chromatin regulation, contributing in the fine tuning of transcription regulation, a major issue of cell differentiation and maintenance of cell identity during development.Key Concepts:Chromatin is a highly structured entity with an important flexibility.The large repertoire of epigenetic modifications offers a wide range of specific molecular and cellular responses.Together with genetic information, epigenetic marks play a critical role in the transmission of gene regulation.Nuclear organisation of chromosomes participates in the inheritance of chromatin states.
Gel Electrophoresis
Authors: Westermeier Reiner 
Published: April 2013

Abstract

Gel electrophoresis is the core separation technique for genetic analysis and purification of nucleic acid fragments for further studies. In an electric field the negatively charged
deoxyribonucleic acid
(DNA) and
ribonucleic acid
(RNA) fragments migrate through a porous gel matrix toward the positive electrode, the anode. Because of the sieving effect of the gel, shorter fragments move faster than larger ones. In this way the DNA or RNA samples are separated according to their molecular sizes into distinct zones, which can be detected by specific visualisation methods. The most frequently used technique is the separation of DNA fragments in agarose gels in simple flatbed boxes combined with the detection of stained bands under ultraviolet light. Polyacrylamide gels are employed, when small fragments have to be analysed or very high resolution down to one single base pair is required. In contrast to capillary electrophoresis the substrate does not need to be prelabelled.

Key Concepts:

With gel electrophoresis very high resolution of nucleic acids can be achieved.

TBE buffer is the standard buffer for DNA and RNA gel electrophoresis.

Agarose electrophoresis is the standard method for DNA restriction fragment analysis and purification of DNA and RNA fragments.

Gel electrophoresis is better suitable for preparative applications than capillary electrophoresis.

Native polyacrylamide gel electrophoresis of amplified nucleic acid fragments is a simple and rapid method for the detection of single‐nucleotide polymorphisms.
Fitness and Selection
Authors: Charlesworth Brian 
Published: April 2013

AbstractSelection affects the genetic composition of a population through differences in fitness amongst genotypes. With discrete generations, fitnesses are usually measured relative to the value for some standard genotype because only relative fitnesses matter. For an autosomal locus with two alleles, when the highest fitness is associated with homozygotes for a particular allele, this allele will spread through the population. When the heterozygote has the highest fitness, a polymorphism is maintained by selection. Variation can also be maintained by frequency‐dependent selection, temporal and spatial variation in fitnesses and a balance between the input of deleterious mutations and their elimination by selection. Selection theory can be extended to more complex situations such as overlapping generations. Selection can act at different levels, including selection among gametes produced by the same individual or amongst groups of individuals. Selection at one site in the genome can also influence evolution and variation at linked sites.Key Concepts:Evolution by natural or artificial selection involves differences in fitnesses amongst genotypes.The fitness of a genotype measures its expected genetic contribution to the next generation.Directional selection at a single diploid genetic locus results in the replacement of one allele at the locus by the alternative allele associated with the fittest homozygote.Balancing selection, such as heterozygote advantage, results in the maintenance within a population of two or more alleles at a locus.Mutations to deleterious alleles occur throughout the genome and contribute to variability before the alleles are removed from the population by selection.Genetic drift in finite populations can cause the loss of beneficial mutations and spread of deleterious mutations.Selection can act at levels of organisation either below or above that of the individual, which may generate conflicts between its effects at different levels.Altruistic behaviour may evolve by kin or group selection.Selection at one site in the genome influences evolution and variation at sites that are genetically linked to it.
Imprinting Disorders
Authors: Henkhaus Rebecca S , Feinberg Andrew P , Niemitz Emily L , Butler Merlin G 
Published: April 2013

Abstract

Genomic imprinting is an example of epigenetic inheritance in which differences in gene function depend on whether the allele was inherited from the mother or father. Many disorders appear to involve epigenetic alterations to imprinted genes. Genes involved in imprinting play important roles in both pre‐ and post‐natal growth and neurodevelopment. Imprinting disorders include several childhood genetic disorders such as Prader–Willi, Angelman and Beckwith–Wiedemann syndromes, as well as several types of cancer including Wilms tumour. Recent evidence suggests a correlation between assisted reproductive technologies (ART) and imprinting disorders, a phenomenon requiring more in‐depth studies as the prevalence of ART is increasing. The mechanism of normal imprinting as well as its perturbation in disease is becoming understood and amenable to experimentation.

Key Concepts:

Imprinted genes are expressed in a parent‐of‐origin‐dependent manner. Imprinting disorders result from genetic abnormalities in imprinted genes.

Approximately 1% of the human genome is imprinted, a process which occurs during gamete development.

Imprinted genes are generally associated with growth, neurodevelopment and epigenetics.

The first imprinted genes discovered were
IGF2
(paternally expressed) and
H19
(maternally expressed), both located at 11p15.

There is an imprinted gene cluster located at 15q11–q13, associated with Prader–Willi and Angelman syndromes. Imprinted genes/transcripts within this region include
NDN
,
MAGEL2
,
SNURF‐SNRPN
,
SNORD116
,
SNORD115
and
UBE3A
.

Well‐characterised imprinting disorders include Prader–Willi syndrome (PWS), Angelman syndrome (AS), Beckwith–Wiedemann syndrome (BWS), Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP), Silver–Russell syndrome (SRS) and transient neonatal diabetes mellitus (TNDM).

Imprinted genes are associated with many types of cancers, primarily due to a process called loss of imprinting (LOI) which leads to aberrant gene expression. Cancers known to be associated with imprinted genes include Wilms tumour in children, and adult cancers of the ovary, lung, colon and liver.

The relationship between artificial reproductive technology (ART) and imprinting disorders is currently being investigated. There is evidence to support a correlation between ART and imprinting disorders which result from loss of maternally imprinted genes such as AS and BWS.
Genetic Imprinting in the Prader–Willi and Angelman Syndromes
Authors: Gurrieri Fiorella , Sangiorgi Eugenio 
Published: April 2013

Abstract

Imprinted genes are expressed from only one of the two parental alleles: they are located in a few, specific chromosomal regions. The parental‐specific expression is obtained through epigenetic modifications (DNA methylation, histone tail modifications) which alter the conformation of chromatin fibre and therefore regulate the expression of the underlying genes. Deletions, duplications, mutations or imprinting defects of the only active allele, as well as uniparental disomy or loss of imprinting of the inactive allele lead to an unbalance (loss of function or gain of function) in the dosage of the gene product and do have phenotypic consequences. Two such examples in human pathology are represented by the Prader–Willi and Angelman syndromes, two phenotypically different conditions, whose phenotypes result from loss of paternal or maternal contribution of the 15q11–q13 genomic region, respectively.

Key Concepts:

Prader–Willi and Angelman syndromes are caused by loss of function of different genes located in a genomic region under the control of a single, bipartite imprinting centre.

These two condition represent the prototype of genomic imprinting disorders in humans.

Genomic imprinting regulates allelic expression according to the parental origin.

Imprinted genes are commonly expressed in half dosage.

Imprinted genes can be inactivated by different mechanisms: uniparental disomy, microdeletion, gene mutation, primary or secondary epigenetic mutation of the imprinting centre.
Mitochondrial Disorders: Nuclear Gene Mutations
Authors: Ghezzi Daniele , Zeviani Massimo 
Published: April 2013

AbstractIn addition to mutations of mitochondrialdeoxyribonucleic acid(mtDNA), many mitochondrial syndromes are due to abnormalities in nuclear genes related to oxidative phosphorylation (OXPHOS). Nuclear genes encode hundreds of proteins directly involved in mitochondrial OXPHOS or linked to other metabolic pathways that are related to OXPHOS, such as the tricarboxylic acid (TCA) cycle and fatty acids β‐oxidation, cell signalling and apoptosis. Although the identification of mutations in mtDNA has become relatively easy because its small size and the nearly complete elucidation of its sequence polymorphisms, the analysis of nuclear disease genes is still a formidable challenge. However, with the recent improvement in technology throughput and bio‐computational power, this scenario is rapidly changing. The discovery of several OXPHOS‐related human genes and the identification of mutations responsible for different clinical syndromes indicate that the majority, but not all, of the inherited mitochondrial disorders are due to nuclear genes encoding proteins targeted to mitochondria.Key Concepts:Mitochondria are the principal intracellular source of energy through the production of ATP by oxidative phosphorylation (OXPHOS).Mitochondria contain their own genome, a small, circular double‐stranded DNA (mtDNA).mtDNA contains 13 genes encoding subunits of the respiratory chain complexes and 24 genes encoding 2 ribosomal and 22 transfer RNAs, which are necessary to carry out intramitochondrial translation.Mitochondria depend on the nucleus for the supply of all of the other OXPHOS proteins as well as the factors necessary for replication, repair, transcription, translation, maintenance of mtDNA and for the biogenesis, shaping, fusion and fission of the organelles.Mitochondrial‐inherited diseases may present with a vast range of symptoms, severity, age of onset and outcome.Because of its dual genetic control, OXPHOS disorders can be due to mutations in mtDNA or nuclear DNA genes.Recent epidemiological studies show that mitochondrial disorders have a minimal prevalence of 1:5 000.
Animal Rights: Animals in Genetics Research
Authors: Wise Steven M 
Published: April 2013

AbstractTo determine whether it should be legal to use a nonhuman animal in genetics research, one needs to evaluate whether she should have the capacity to possess any legal right at all, that is, whether she should be deemed a ‘legal person’, as a matter of liberty, equality or both. The key trait is dignity and what I call ‘practical autonomy’. If a nonhuman animal has the capacity to possess any legal right, the issue is then whether she should be entitled to such fundamental legal rights as bodily liberty and bodily integrity, and whether she should have the legal right to sue to enforce those rights.Key Concepts:Legal personhood is the fundamental building block of legal rights.Legal persons have the capacity to possess legal rights.Who should be a legal person is a matter of principle and not policy or precedent.One may argue for legal personhood either a noncomparative or as a comparative right.Practical autonomy is a sufficient condition for legal personhood as a noncomparative right.One has practical autonomy if one can desire, intentionally try to fulfil that desire, and possesses a sense of self‐sufficient to allow one to understand, even dimly, that it is oneself who wants something and is trying to get it.The more exactly members of a nonhuman species resemble humans in behaviour, and the closer they are to humans taxonomically, the more confident we can be that they possess practical autonomy.The Normative Model of equality is a hybrid of a comparative and a noncomparative right, as it determines rights against a larger social, political and legal backdrop. It seeks to identify whether some rational connection exists between the means used to accomplish an end and the end it seeks to accomplish and makes a judgement about whether the end itself is appropriate.Prohibited ends might include a legislative or judicial classification that burdens a plaintiff in a manner that reflects deeply personal social stereotypes that are biologically immutable or changeable only at unacceptable personal costs or that involve morally irrelevant traits.A Level 1 legal person may possess any of an infinite number of legal rights, again as a matter of liberty and equality.