bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centromeric Sequences and Sequence Structures
Authors: Koch Jørn , Andersen Anni 
Published: April 2013

Abstract

Centromere function is essential for the faithful passing on of the parental genome to daughter cells in cell division. This function is carried by specialised noncoding
deoxyribonucleic acid
(DNA), centromere DNA. The functional DNA element in human centromeres is the α‐satellite DNA, which we share with all other primates, but not with nonprimate species. This DNA acts through timed interactions with proteins belonging to the cell‐cycle machinery, such as topoisomerase II, which cuts the interconnecting bridges between sister‐chromatids to allow and enable the completion of mitotic and second state meiotic cell divisions. To orchestrate these interactions, centromere DNA has the ability to fold into complex three‐dimensional shapes, which are the form of the DNA recognised by its protein partners.

Key Concepts:

Unlike genes coding for proteins, noncoding DNA is not coded in a triplet code where each triplet can be translated into a specific amino acid.

Noncoding DNA is instead coded in the form of spatial structures capable of governing specific interactions with DNA, RNA and proteins in ways that are more reminiscent of antigen–antibody reactions than of the triplet coding.

For this reason scientists have had a hard time understanding what noncoding DNA is good for, at some point even leading to the misconception that it served no good function, but merely was ‘selfish DNA’.

With the discovery of the noncoding RNAs, which are very important for gene regulation, a very different picture is now dawning, and we trust that it will end in the understanding that genes are nothing more than ‘stupid’ data files, whereas the rest of the genome is ‘the software’ reading those data files to produce ‘the hardware’ in the form of gene products.

Centromere DNA is one species of noncoding DNA. It serves its functions through interactions with a whole range of DNA‐binding proteins, and to enable the interactions to be ‘on’ or ‘off’ as appropriate, the DNA must be able to turn into different shapes and forms, which are recognised, or not recognised by the various proteins.
Polyploid Origin of the Human Genome
Authors: Kasahara Masanori 
Published: April 2013

Abstract

Accumulated evidence indicates strongly that two rounds of whole‐genome duplication (2R‐WGD) took place in the vertebrate lineage after its separation from invertebrate chordates; hence, the human genome can be regarded as paleooctoploid. The vertebrate genome often contains closely linked sets of paralogous genes (paralogues) on typically four different chromosomes. This genome architecture is widely believed to reflect the remnants of 2R‐WGD. In honour of Susumu Ohno, who initially proposed that the vertebrate genome underwent one or two rounds of tetraploidisation, paralogues that arose by 2R‐WGD are called ohnologues. Only 15% to 30% of human genes are members of the ohnologue families, indicating that most of the duplicated copies generated by 2R‐WGD were lost. Preferentially retained after WGD are dosage‐sensitive genes such as those encoding components of the complex biological machines or cascades.

Key Concepts:

2R‐WGD took place in the vertebrate lineage after its separation from invertebrate chordates.

The strong evidence supporting 2R‐WGD is the occurrence of closely linked sets of paralogues on typically four different chromosomes.

WGD enabled duplicated genes to coevolve efficiently, thus leading to the formation of gene networks required for biological innovations.

After gene duplication, one of the duplicated copies becomes redundant and usually begins to accumulate deleterious mutations, resulting in its eventual loss.

An important requisite for the retention of duplicated genes is their divergence to acquire new functions or to partition the functions of their ancestral gene.

Dosage‐sensitive genes tend to be preferentially retained after WGD.
Exons and Protein Modules
Authors: Patthy László 
Published: April 2013

AbstractModules are versatile protein domains that are frequently used as building blocks in the construction of diverse multidomain proteins. The degree of versatility or promiscuity of protein modules is usually defined as the number of distinct domain architectures in which they are present or the number of domain types with which they are associated in diverse multidomain proteins. The assembly of multidomain proteins from modules is facilitated by recombination in introns flanking the exons that encode the modules, but it may also occur by recombination in exons or through cotranscription and fusion of tandem genes. Protein modules that frequently participate in domain‐shuffling events (that is, moved from one genomic location to the other) are usually referred to as mobile domains.Key Concepts:Domain types that are frequently used as building blocks of multidomain proteins are usually referred to as protein modules.The degree of versatility or promiscuity of protein modules may be defined as the number of distinct domain architectures in which it is present or the number of domain types with which it is associated in diverse proteins.Protein modules that frequently participate in domain‐shuffling events (that is, moved from one genomic location to the other) are usually referred to as mobile domains.Protein modules flanked by introns of identical phase are exceptionally mobile because their shuffling is facilitated by intronic recombination.Although assembly of multidomain proteins from modules is facilitated by recombination in introns it may also occur by recombination in exons.
Children in Genetic Research
Authors: Alderson Priscilla 
Published: April 2013

AbstractGenetic research offers potential benefits and harms to children. Respect for children's individual and collective best interests, and for their human rights and worth and dignity includes keeping them informed, and involving competent children as much as possible in making decisions about genetic research that affects them. Their privacy and identity must be respected, as well as the consent or refusal of parents and of competent children. The article reviews theDeclaration of Helsinkiand other ethical guidance, as well as differing standards for research with children between Britain and the USA. The term ‘therapeutic research’ is critically analysed, and also questions of justice and who bears the burdens or enjoys the benefits of genetic research in richer and in poorer countries. Research with children about dominant and recessive, autosomal and sex‐linked genetic conditions, about multigenetic predisposition meaning causally heterogeneous and often complex in origin, genomics and epigenetics, gene therapy and nature versus nurture, attention deficit hyperactivity disorder (ADHD) and economic influences is discussed.Key Concepts:Genetic research includes investigation into how children's traits, anomalies, behaviour or disease might be influenced by genomics, or by epigenetics, how this knowledge can be applied and shared, and how interventions to detect, treat and prevent adverse genetic conditions can be developed.Research ranges from the study of conditions associated with single genes in closed predictable systems, to multigenetic predispositions interacting with many environmental influences.The differing influences of genes and environment and their complex overlapping and interactions are debated, particularly regarding behavioural conditions.When exploring connections between genotypes and phenotypes (ways in which genes are expressed) researchers also need to know about children's social contexts.There are risks that genetic researchers overstate the value and influence of their knowledge on health, and confuse giving information with providing therapy.Children and adults tend not to accept advice to alter their life‐style significantly in order to reduce or prevent symptoms of a genetic condition.Research about gene therapy incurs risks and has not yet provided tested or proven effective treatments.Children should be involved in genetic research only if the findings are intended to benefit them and cannot be obtained from an older age group.Economics crucially influences all stages of genetic research in the selection of topics, the funding and scale of projects, promotion of reports and implementation of findings.Social justice requires that the groups of children who take part in research, including those in poorer countries, should also be able to benefit from the findings.
deCODEand Iceland: A Critique
Authors: Árnason Einar , Andersen Bogi 
Published: April 2013

AbstractdeCODE Genetics Inc. was a for‐profit American corporation built around the idea of cloning and characterising the genes of Icelanders and marketing the information so obtained through a central database containing health information, genetic information and genealogy. deCODE's database plan in Iceland brought into focus business practices of the genomics industry and a number of ethical issues. The company promoted and sold its shares to the public in Iceland through a ‘grey market’ before its initial public offering, leading to large investment losses for common Icelanders with little investment experience. The law permitting the health sector database was found unconstitutional and the company never built the controversial database. Instead it pursued traditional genome‐wide association studies attempting to identify genetic changes contributing to common diseases. Through this work, the company created a large database and contributed a large number of scientific papers, but was a commercial failure going bankrupt in 2009. After a stalking‐horse sale it rose from the ashes and continued operation as a private company under almost the same name, focusing on whole genome sequencing data to understand common diseases and human variation. At the end of 2012, Amgen announced that it would pay $415 million to acquire deCODE. The sale price was based on a product derived from an Icelandic resource but no compensation was given to the Icelandic people.Key Concepts:deCODE was founded on the belief that unifactorial methods of searching for identity by descent in extensive pedigrees, so important in searching for Mendelian traits, would yield the genetics of common disease.The genetic variants in most current GWA studies only explain a portion of the heritability.Multiple variants, each with a small effect, seem to contribute to common diseases.Rare genetic variant conferring a larger effect may also contribute to common diseases.As a foundation for a commercial company, the identification of genetic variants in common disease was a failure for deCODE Genetics.deCODE lays claim to a number of scientific papers but turning the science into a profitable busienss failed.deCODE Genetics Inc. employed questionable business practices when raising funds from the public in Iceland.The health sector database law in Iceland was found to be unconstitutional and deCODE Genetics never built the database on which its initial public offering was based.deCODE Genetics Inc. declared bankruptcy but rose from the ashes after a stalking‐horse sale to a company partly owned by some of initial investors and by sequencing giant Illumina. It now operates under the name deCODE Genetics ehf. In December 2012 deCODE was purchased by Amgen and is now operated as a wholly owned Amgen subsidiary.
Patenting of Genes: Discoveries or Inventions?
Authors: Gold E Richard 
Published: April 2013

Abstract

Since the 1980s, patent offices in most developed countries (with some exceptions, particularly in Latin America) have been granting patents over both genomic and modified
deoxyribonucleic acid (DNA)
sequences based on the legal understanding of the difference between invention and discovery, which does not necessarily accord with the same concepts among scientists. Recent litigation in USA has, however, cast uncertainty over this conclusion, particularly with respect to genomic DNA sequences. Patents over the process of using these sequences to identify the risk of contracting a disease is even more uncertain. Controversy continues over the role that both DNA sequence and associated method patents play in encouraging innovation. This is particularly true in clinical genetics in which the patent holder is rarely the first to make a genetic test available to patients.

Key Concepts:

The legal understanding of the difference between an ‘invention’ and a ‘discovery’ does not correspond to how scientists appreciate the difference.

Patent offices in most developed countries have been granting patents over both DNA sequences (in both genomic and modified form such as cDNA) and methods of using them since the 1980s.

Only recently have these been challenged in court in USA with uncertain results.
China: The Maternal and Infant Health Care Law
Authors: Guo Sun‐Wei 
Published: April 2013

Abstract

The Law of the People's Republic of China on the Maternal and Infant Health Care (MIHCL), enacted in 1995, sparked widespread concerns, criticisms and in some cases fierce outcries in the Western scientific community. This article describes the background in drafting the law, chronicles reactions to its release and its subsequent development, attempts to provide a balanced presentation on perspectives of the West and of Chinese side, draws up a list of questions surrounding this controversy and its subsequent development, and, finally, argues that the entire process holds several lessons to future legislature in China when drafting health‐related laws.

Key Concepts:

The Law of the People's Republic of China on the Maternal and Infant Health Care (MIHCL) was enacted in 1995.

The law was drafted apparently in response to enormous population pressure, the heavy burden of people with disability, and questionable local practices that restrict reproductive freedom on people with mental and putative hereditary diseases.

The law sparked widespread concerns, criticisms, and in some cases fierce outcries in the Western scientific community, yet experts in China defended the law.

The most contentious articles in the law include ones that propel physicians to provide medical advice on long‐term contraception or sterilisation to couples who have been diagnosed with unspecified genetic disease of a serious nature after a mandatory pre‐marital medical examination (PMME).

In 2001, the Implementation Methods of MIHCL went effective, in which articles in the MIHCL that aroused controversies were written in a manner that is more ‘politically correct’ by Western standards.

In 2003, the Ministry of Civil Affairs issued The Marriage Registration Code, which effectively abolished the mandatory requirement for PMME as a prerequisite for marriage registration.

This dramatic change, viewed by many as inconsistent with the MIHCL, received warm welcome from the public, many of them unhappy with the mandatory requirement for PMME, but it also raised concern that the abolishment may have resulted in increased incidence of birth defects.

In 2005, a special Task Force reached conclusions that there is no credible evidence that suggests that the rising incidence of birth defects in some areas can be attributable to the abolishment of compulsive PMME and that the PMME has limited value in preventing birth defects.

The enactment of MIHCL and the subsequent, somewhat dramatic reverse in course beg for many questions regarding the scientific basis, if any, for the legislature.

The controversy surrounding the MIHCL and its subsequent development hold several lessons for people who attempt to solve complex health‐related problems through judiciary means.
Intellectually Disabled in Britain: Sexuality and Procreation
Authors: McCarthy Jane , Sinason Valerie , Hollins Sheila 
Published: April 2013

Abstract

Ethical and social issues surround the issue of sexuality and parenting for people with intellectual disabilities. The traumatic history of eugenics is encapsulated in Nazi Germany's description of those with intellectual disability as unworthy of life and the 250 000 children and adults who were gassed but conscious and unconscious wishes to deny sexual and procreative rights to those with an intellectual disability is world‐wide and contemporary despite legislative change. However, given the high levels of sexual abuse and exploitation that come from internal and external stigmatisation and trauma the movement towards greater human rights, sexual education and access to psychotherapy heralds new hope for children and adults with an intellectual disability and the wider community.

Key Concepts:

In working with people with intellectual disability on the themes of sexuality and procreation a multi‐disciplinary approach is needed.

Ethics, human rights, genetics and psychotherapy are all relevant in working with sexuality and procreation in people with intellectual disability.

A history of trauma and eugenics is a necessary prerequisite to understanding the controversial topic of disability, sexuality and procreation.

Co‐operation with geneticists is important in considering procreation and disability.

People with an intellectual disability have a right to their own sexuality.
Preimplantation Genetic Diagnosis: Ethical Aspects
Authors: Juth Niklas 
Published: April 2013

AbstractPreimplantation genetic diagnosis is a procedure, which allows for the selection between embryos before the initiation of pregnancy. Although considered morally controversial, for example, depending on views regarding the moral status of embryos, this procedure seemingly reduces ethical problems in prenatal diagnosis by offering the possibility of selecting offspring without the need to consider abortion. However, counselling of patients becomes more complicated. Also, there are controversies regarding who should be the primary beneficiary, for instance when an embryo is chosen partly to be a suitable tissue donor to a sibling, as well as regarding when benefits outweighs downsides. Moreover, preimplantation genetic diagnosis raises concerns about the connection between the pre‐selection of children on genetic grounds and the discrimination of disabled people. It also raises the ethical problem of whether the selection of future children on the basis of less serious or even nonpathological traits is an acceptable practice.Key Concepts:Preimplantation genetic diagnosis (PGD), selecting embryos based on genetic analysis before pregnancy byin vitrofertilisation (IVF), gives rise to ethical issues on the basic, clinical and societal level.The acceptability of PGD depends on how one views parental responsibilities towards future children and the moral status of embryos.Prospective parents may consider PGD to be preferable to prenatal genetic diagnosis, since in PGD selection can be made without subsequent abortion.Drawbacks of PGD may outweigh benefits if the procedure of IVF is considered too burdensome, if the pattern of heredity is considered too complex to yield unambiguous genetic information, or if the condition is not considered serious enough.PGD may also be used to select embryos that can become suitable bone marrow donors to seriously ill siblings, which has aroused controversies regarding the instrumentalisation and future well‐being of these children.PGD makes genetic counselling more complex and possibly harder to comply with the ideal of nondirectiveness.The question of which uses of PGD should be allowed can only be answered against the background of the basic ethical issue of what goal PGD should be taken to serve.The goal of promoting reproductive autonomy gives rise to ethical issues of using PGD for less serious conditions or nonpathological traits, which may lead to backdoor eugenics.The goal of preventing (the birth of individuals with) certain serious diseases gives rise to ethical questions of which diseases should be considered serious enough, as well as concerns of a subsequent reinforcement of discrimination and stigmatisation of disabled people.The idea of a list of pre‐defined conditions serious enough for PGD sends the message that people affected by these conditions are more undesirable than others, which may push the situation closer to morally problematic forms of eugenics.
Personality and Temperament
Authors: Gagne Jeffrey R 
Published: April 2013

Abstract

Temperament is an early developing set of characteristics related to later personality. Commonly studied dimensions of temperament include activity level, anger/frustration, behavioural inhibition/fear, effortful control and positive affect. Personality includes a range of traits, including major traits of extraversion, neuroticism and impulsivity/sensation‐seeking. Different aspects of personality and temperament are related to important developmental outcomes such as behavioural problems and psychopathology. Both behavioural genetic and molecular genetic research have contributed to the understanding of major traits of temperament and personality. Behavioural genetic approaches use twin and adoption study designs to estimate genetic and environmental contributions to individual differences in traits. Most behavioural genetic studies have found substantial heritability for personality and temperament. Molecular genetic investigations focus on the effects of specific genes (primarily dopamine‐ and serotonin‐related genes in studies of temperament and personality).

Key Concepts:

Rothbart's broad extraversion/surgency, negative affectivity and effortful control dimensions of temperament are related to three of the Big Five personality factors: extraversion, neuroticism and conscientiousness, respectively.

The results of twin and adoption studies have shown significant genetic and nonshared environmental variance in temperament and personality.

Contemporary researchers investigating personality and temperament from a molecular genetic standpoint typically use either candidate gene studies or genome‐wide association studies (GWAS).

Although behavioural and molecular genetics are separate fields, most behavioural genetic researchers have begun incorporating molecular techniques into their research programs.

Genotype–environment interactions, genotype–environment correlations and endophenotype approaches are utilised in genetic studies of temperament and personality.

Candidate gene studies of dopaminergic and serotonergic genes have informed ongoing molecular genetic research in temperament and personality.

Increasingly, studies of other candidate genes as well as GWAS approaches are also extant in the literature.