bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence Finishing
Authors: Beasley Helen , Grafham Darren , Willey David 
Published: April 2013

Abstract

Sequence finishing can be described as the manual enhancement of assembled shotgun sequence data to improve regions of low quality or close gaps in the sequence. Shotgun sequencing data can be whole genome derived or from clone‐based entities such as bacterial artificial chromosomes (BACs) or other plasmid based vectors such as fosmids. Sequence finishing can be achieved using a combination of laboratory and computational techniques to produce a highly accurate and complete deoxyribonucleic acid (DNA) sequence.
Variable coverage and sequence gaps can occur across whole genome shotgun or a particular BAC or fosmid owing to the random nature of shotgun sequencing and the composition of a given piece of DNA can be prohibitive to both the cloning and sequencing process. A targeted approach is required to provide a more cost effective means of improving any regions of low quality and to close gaps that remain after initial shotgun sequencing.

Key Concepts:

Gaps exist in shotgun sequence for various reasons including structural elements, which can interrupt the sequencing reaction and variation in coverage owing to chance.

Directed finishing to close gaps in shotgun DNA sequence is labour intensive compared with high throughput shotgun sequence generation.

Good quality complete DNA sequences facilitate genome annotation and comparative sequencing studies.
Adoption Studies
Authors: Yates William R 
Published: April 2013

Abstract

Adoption studies are one form of clinical genetic study designed to evaluate genetic and environmental influences on phenotype. In adoption studies the index cases and controls are adoptees. The adoption study design provides a unique opportunity to examine gene and gene by environment interactions for a variety of behavioural, psychiatric and medical disorders. Adoption genetic studies provide some challenges related to the issues related to adoption (atypical biological parent profiles, differences in adoptive parents compared to nonadoptive parents and the stress of learning about being an adoptee). Recently, molecular genetic strategies have been applied to samples of adoptees. Advancing privacy issues have made it more difficult to design and carry out adoption research.

Key Concepts:

Adoption studies provide a unique research model where biological genetic effects can be estimated.

Adoption studies can be helpful in uncovering gene–environment interactions in complex behavioural and psychiatric disorders.

Adoption genetic studies utilise a variety of statistical techniques including calculation of odds ratios, logistic regression, log‐linear statistical monitoring and path analysis.

Recent advances in adoption study research have occurred by combining molecular genetic techniques to the genetic and environmental data of adoptees.

Increased privacy concerns and privacy laws related to biological parent anonymity have made adoption studies more difficult to design and implement.
Metabolism: Hereditary Errors
Authors: Groop Leif , Rosengren Anders 
Published: April 2013

Abstract

Inherited metabolic diseases can be both monogenic and polygenic. The monogenic forms are usually rare and are characterised by early onset. Examples include maturity‐onset diabetes of the young (MODY), phenylketonuria and
glycogen
storage diseases. The polygenic metabolic diseases result from a complex interaction of genetic variants and environmental factors. Type 1 and type 2 diabetes are typical examples. Important progress has been made in unravelling the genetic background of the common forms of diabetes. For type 2 diabetes, close to 50 loci have been consistently associated with increased disease risk. The findings have provided novel pathophysiological insights and suggest that type 2 diabetes occurs when the pancreatic islets fail to compensate for the increased insulin demands in states of insulin resistance. The exact disease mechanisms associated with the genetic variants are however in most cases not completely known. Novel approaches, including
deoxyribonucleic acid (DNA)
sequencing, are likely to give a more comprehensive picture of the genetic background.

Key Concepts:

Genetic factors play an important role in most metabolic disorders.

Monogenic metabolic diseases such as MODY have high penetrance and early onset.

The common metabolic disorders have typically a polygenic inheritance.

Type 1 and type 2 diabetes have a complex pathogenesis and result from a combination of environmental and genetic factors.

Genome‐wide association studies have identified a large number of disease susceptibility variants for type 2 diabetes.

Identification of genetic risk variants is invaluable for improving the pathophysiological understanding.
Digenic Inheritance
Authors: Vockley Jerry 
Published: April 2013

AbstractMonogenic inheritance refers to genetic control of a phenotype or trait by a single gene. For a monogenic trait, mutations in one (dominant) or both (recessive) copies of the gene are sufficient for the trait to be expressed. Many traits are not determined so simply, and either involve the interaction of many genes with (multifactorial inheritance) or without (polygenic inheritance) environmental effects. Less commonly, the interaction of only two genes is required for expression of a phenotype, a mechanism referred to as digenic inheritance. In this situation, mutations in at least one copy of each gene are required for the expression of a phenotype. A growing number of human diseases with a digenic inheritance pattern are being described, a phenomenon that is likely to increase with moredeoxyribonucleic acid(DNA) sequence data being generated through clinical‐based exome and genome sequencing efforts.Key Concepts:Traditional mendelian patterns of inheritance are controlled by mutations at a single genetic locus.Many human disorders are caused by more complex patterns of inheritance.Digenic inheritance refers to mutation on two genes interacting to cause a genetic phenotype or disease.Triallelic inheritance is a special case of digenic inheritance that requires homozygous mutations at one locus and heterozygous mutations at a second locus to express a phenotype.Digenic inheritance is probably best though of as being on a continuum that includes modifier effects of monogenic inheritance and polygenic or multifactorial inheritance.
Racism, Ethnicity, Health and Society
Authors: Bradby Hannah 
Published: April 2013

Abstract
Racialised thinking about human diversity underlies some infamous medical and scientific abuses, although in some cases the form of discrimination is cloaked in the language of ethnicity. A central dilemma of measuring equity along the lines of ethnicity is that categories of difference are inevitably reinforced. Although measuring iniquity may facilitate its redress, it may also reify and reinforce categories which are the basis of discrimination. The role of historical manifestations of racism in the case of rickets and sickle cell disease are discussed. The compounding of racialised disadvantage with other forms of marginalisation is discussed in terms of individual and institutional discrimination with regard to the origins of the HeLa cell line.
Heredity and the Novel
Authors: Davis Lennard J , Jarman Michelle 
Published: April 2013

Abstract

The concept of heredity, as represented throughout the history of the novel, may be further illuminated by certain discoveries of the modern science of genetics. Since the novel's origin, authors have explored cultural beliefs and anxieties around heredity, nobility, bloodlines, birthrights and ‘tainted’ lineages. As modern genetics grows increasingly sophisticated, novelists engage in more complex ethical questions ranging from genetic selection and manipulation to reproductive choice and hereditary ‘rights’. In science fiction genres, themes can expand into human enhancement, species destruction and creation. Yet even as contemporary works engage in the complex new science and bioethical questions that grow out of genetic research, contemporary writers remain fundamentally interested in exploring what genetic knowledge and technology means within the context of intimate human relationships.

Key Concepts:

Since the origin of the novel, authors have engaged with hereditary themes.

Changing historic notions about heredity are reflected in novels of those periods.

Works of literature are important sites of investigation into public perceptions of emergent scientific ideas about heredity.
Deaf Community and Genetics
Authors: Middleton Anna , Emery Steve , Palmer Christina , Boudreault Patrick 
Published: April 2013

AbstractThe Deaf community consists of a group of like minded people sharing a common sign language and culture. This community has a positive attitude toward being deaf. Typically, deafness is considered a strong part of linguistic and cultural identity and Deaf individuals do not wish to have treatments or a cure.Deaf people have concerns that a hearing society, with little knowledge or experience of their rich culture and language, would encourage the use of pre‐implantation genetic diagnosis and prenatal genetic testing for deafness with the ultimate aim of having hearing children. They feel strongly that deafness is a source of human variation that does not warrant the use of genetic technology in this way. Deaf (written with an uppercase 'D') refers to people who belong to the Deaf community. Deaf people use sign language (e.g. British Sign Language, American Sign Language, Auslan, etc.) as their first or preferred language. They also have a positive identity attached to being Deaf. People who consider themselves deaf (written with a lowercase 'd') or hard of hearing tend to use speech as their preferred form of communication, and may experience being deaf as a medical disability that needs to be treated. These groups often have very differing attitudes towards the use of genetic technology.Key Concepts:Deaf people often do not mind if their children are deaf or hearing; whereas hearing or hard of hearing people typically prefer to have hearing children.Genetic technology can be used to reduce the number of deaf children born, for example, via the use of preimplantation genetic diagnosis with a selection of embryos that contain the genes for hearing or via the use of prenatal genetic diagnosis where a termination of pregnancy is offered if the baby is found to have the genes for deafness.There is a serious concern amongst the Deaf community that genetic technology will be ‘misused’ by hearing people to select against deafness. If significant number of people choose to use genetic technologies to facilitate the selection of hearing children then they fear that this will result in decline of the Deaf community.If fewer deaf babies are born, Deaf people recognise that this may result in a decimation of their language and culture, and an increasing disregard for the rights of self‐determination of deaf individuals.Being deaf can arise as a result of different factors, genetics is only one of these. It is likely that there will always be environmental causes, newly arising genetic causes, and people who do not use genetic technology for diagnostic purposes, and so there will always be D/deaf people in society.
Personal Identity: Genetics and Determinism
Authors: Chadwick Ruth 
Published: April 2013

Abstract

Traditional theories that locate the identity of the human person in physical or psychological attributes are subject to reinterpretation in the light of advances in genetics. A person's genome may be regarded as the ‘essence’ of the person, or as the foundation of specific characteristics that are central to a person's identity. A view that there is no such thing as ‘essence’ may still give genes an important role to play in constructing a person's biography, both as regards the past (ancestry tracing) and the future (e.g. future health status). Collective identity is also an issue, in terms of common origin or disease groupings. Developments in direct to consumer testing and whole genome sequencing have the potential to reinforce both the importance accorded to the genome, and genetic determinism.

Key Concepts:

There is a wide range of views about the importance of genes to personal identity.

In a physical account of identity, genes offer a consistent basis for identity throughout many changes to an individual, but present problems in the case of division.

In a psychological account of the person, while genes may be relevant in setting the parameters within which a person develops, this should not be taken to justify a reductionist view of genes and identity.

On a constructivist account, individuals’ self‐perceptions may be influenced by genetic information. This is likely to grow in importance as personalised genetic information becomes more widely accessible.

If personal identity is tied up with genes, questions of identity will come to the fore in discussions of gene therapy.

Developments in direct to consumer testing and whole genome sequencing have the potential to reinforce both the importance accorded to the genome, and genetic determinism.

Although genetic determinism was claimed to be dead upon the completion of the human genome project, current developments such as genetic ancestry testing hint at a resurgence of a popular belief in a meaningful identity buried deep within the genetic code.
Addiction and Genes: Animal Models
Authors: Phillips Tamara J , Gubner Noah R 
Published: April 2013

Abstract

Genes influence susceptibility to alcohol and drug dependence. The sequence of a gene may differ among individuals, and each gene form (or allele) may produce a different product (i.e. a different form of a protein, such as an enzyme, receptor or hormone). Differences in gene sequence or polymorphisms are one source of individual differences in risk for addiction. In addition, individuals with the same form of a gene may express the gene product in different amounts, and this may be another source of differential risk. Genetic animal models are used to study genetic influence and identify addiction‐relevant genes. These include classical genetic models, such as standard inbred strains and selected lines, and newer era genetic models and techniques such as transgenics, knockouts, microarray analysis, next generation sequencing and optogenetics. These genetic models are important tools used to identify factors that influence risk for addiction and mechanisms that could lead to novel treatments.

Key Concepts:

Addiction is not a single gene trait (also known as a Mendelian trait) like Huntington's disease or sickle‐cell anaemia.

Each gene that influences addiction may have a relatively small influence but together can account for a significant amount of the variation among people in risk for addiction.

The newest tools used to explore the genetics of addiction have benefited from the complete sequencing of the human genome and the genome of several other species.

Successful selective breeding indicates that there is genetic influence on the measured trait.

Bidirectional genetic research occurs when animal studies lead to investigation of similar genetic factors in humans and vice versa.

Optogenetics is a relatively new and exciting procedure for controlling brain activity with light using specific genetic manipulations.
Mitosis and Meiosis: Molecular Control of Chromosome Separation
Authors: Nagasaka Kota , Gallego‐Paez Lina M , Hirota Toru 
Published: April 2013

Abstract

Accurate chromosome segregation during both mitosis and meiosis is governed by an intricate and synchronised cascade of events. These are controlled by the molecular networks that ensure the proper assembly of sister
deoxyribonucleic acid
(DNA) molecules produced during DNA replication, followed by the action of the spindle that pulls the sister chromatids apart. Mistakes in these processes would lead to chromosome transmission defects and subsequent aneuploidy, a common hallmark of many tumour cells. Herein, we review recent progresses in the molecular illustration of the chromosome architecture and function specially those depending on the structural maintenance of chromosome family of protein complexes, in conjunction with the spatio‐temporal regulation of cell‐cycle progression.

Key Concepts:

Cohesin is the glue that entraps duplicated sister DNA.

DNA replication is coupled to the establishment of sister‐chromatid cohesion through cohesin acetylation.

The bulk of cohesin is removed from chromosome arms by phosphorylation in early stages of mitosis, whereas centromeric cohesin is removed by separase‐mediated cleavage at the metaphase anaphase transition.

Condensin is required for a proper mitotic chromosome assembly.

Smc family of protein complex determine chromosomal structure and function throughout the cell cycle.

Separase is tightly regulated in cell cycle and become active exclusively at the onset anaphase.

SAC monitors the presence of unattached kinetochores.

Protein degradation mediated by the APC/C drives anaphase onset.

Back‐to‐back orientation of kinetochores is required for Meiosis II and mitosis, whereas, side‐by‐side orientation of kinetochores is required for meiosis I.

Shugoshin protects precocious dissociation of cehesin.

Bi‐orientation of chromosomes depends on the correction mechanisms and spindle assembly checkpoint.
Severe Combined Immune Deficiency (
SCID
): Genetics
Authors: Fischer A 
Published: April 2013

Abstract

Severe combined immunodeficiency consists of an array of genetically determined blocks in T‐lymphocyte development. Characterisation of genetic defects contributes to a better understanding of lymphocyte differentiation pathways. Seventeen distinct defects have now been characterised that affect multiple steps of T lymphocytes ontogenesis, from defective survival of several haematopoietic lineage precursors, premature cell death of lymphocyte precursors, defective interleukin‐7‐dependent survival/proliferation of T‐lymphocyte precursors, defective recombination of T‐cell receptor (TCR) genes, defective (pre) TCR signalling and defective egress of the thymus. These disorders are life threatening because of the early onset of various infections notably caused by opportunistic agents, hence stressing the importance of T cell adaptive immunity in longevity. These disorders can be cured by allogeneic haematopoietic stem cell transplantation, some by gene therapy while neonatal screening is being developed.

Key Concepts:

Severe combined immunodeficiencies are rare inherited diseases caused by defective development of the T lymphocyte lineage.

Clinical consequences are devastating leading to death within the first year of life in the absence of treatment.

Allogeneic transplantation of haematopoietic stem cells or in some cases gene therapy can be life saving by restoring T‐cell development.

Seventeen different genetic defects have been found to cause SCID, they are classed in six groups as based on pathophysiology.

SCID variants – defined by the presence of residual T cells – are relatively frequent as a consequence of hypomorphic mutation or reversion.
Public Health Genomics
Authors: Zimmern Ronald L 
Published: April 2013

Abstract

Public health genomics is a subspecialty within public health that deals with the application of genetics, genomics and molecular science to the promotion of health and the prevention of disease. Its subject matter is multidisciplinary in scope and requires an understanding not just of scientific advances, but also the population sciences, biostatistics and epidemiology, and the humanities and social sciences. Its fundamental concept is that genetic variation is an important determinant of health, and that all human traits and pathology come about as a consequence of the combined effects of genetic and environmental factors. These considerations have important implications for the future practice of public health across all its roles: health protection, health promotion and the development and organisation of health services. Its impact is not only just on inherited disorders, but also across the entire range of infectious and noncommunicable diseases. Public policy and regulatory frameworks will need to be adapted to ensure the responsible implementation of genome‐based knowledge and technologies within society.

Key Concepts:

Public health genomics is multidisciplinary, with its knowledge base deriving from not just genetic and molecular science, but also from the population sciences, the humanities and social sciences.

Public health genomics relies on understanding that genetic variation is an important determinant of health, and that all human traits and pathology comes about as a consequence of the combined effects of genetic and environmental factors.

The mission of public health genomics is to improve population health through the use of knowledge and technologies in an effective and responsible manner.

Public health professionals must ensure that they understand the part played by genetic variation and other molecular and cellular processes, and how that understanding can be used to contribute to the health of individuals and populations.

Training and education, improving the utility and efficiency of research, ensuring safe and effective services and technologies, supporting the development of relevant public policy and of health service provisions are all essential activities within public health genomics.
Spinal Muscular Atrophy
Authors: Farrar Michelle A , Kiernan Matthew C 
Published: April 2013

Abstract

Spinal muscular atrophy (SMA) is a relatively common neurodegenerative disease marked by muscle weakness and atrophy due to degeneration of motor neurons of the spinal cord and lower brain stem. The most common form of SMA is caused by homozygous disruption of the survival motor neuron 1 (
SMN1
) gene on chromosome 5q and results in insufficient levels of SMN protein in motor neurons. There is a broad spectrum of clinical severity, which inversely relates to the number of copies of the
SMN2
gene. Although advances in the understanding of the disease biology have provided therapeutic targets, no effective disease modifying treatment is currently available. Promising therapeutic strategies include utilising the unique genomic structure of the
SMN
genes to increase SMN protein transcripts, neuroprotective agents, gene therapy and stem cell transplantation.

Key Concepts:

The most common form of SMA is secondary to homozygous disruption of the
survival motor neuron 1 gene
(
SMN1
) located on chromosome 5q13 and results in insufficient levels of survival motor neuron (SMN) protein in motor neurons.

SMA is classified into three common types based on age of onset and maximal motor milestones attained (Munsat and Davies, 1992): SMA type 1 has onset within the first 6 months and patients do not sit without support; SMA type 2 patients manifest weakness after 6 months of age and the maximum motor milestone is the ability to sit; SMA type 3 patients attain the ability to walk.

The clinical spectrum of SMA is broad, ranging from early infant death to normal adult life with minimal weakness.

The diagnosis of SMA is based on molecular genetic testing. Approximately 95% of individuals with SMA are homozygous for a deletion of
SMN1
and 5% may reflect compound heterozygotes.

In humans there is an almost identical copy of the gene,
SMN2
, which predominantly encodes a truncated form of the SMN protein that is rapidly degraded. Functional ability inversely relates to
SMN2
copy number.

Current management incorporates multidisciplinary care and focuses on preventing and addressing the complications of weakness and promoting quality of life.

Advances in the understanding of molecular pathogenesis of SMA have provided novel therapeutic targets, however translation has held limited success to date.