bluuebunny/crossref_metadata_2025 huggingface dataset:
Tiering in the Sea – Reefs and Burrows (Late Palaeozoic)
Authors: Wood Rachel A
Published: September 2010

Tiering is often considered as a proxy for the ecological complexity of ancient communities. Ancient reefs in the Late Palaeozoic were dominated by microbial communities that formed complex substrate topographies, together with a variety of calcified algae and suspension‐feeding metazoans that populated open and cryptic surfaces. Tiering in epifaunal communities increased significantly in the Ordovician to form complex tiered communities that persisted throughout the Palaeozoic. By contrast, infaunal tiering developed slowly, with occupation of deeper depths being achieved only by the Lower Carboniferous.

Post‐Permian mass extinction epibenthic and infaunal biotas were of very low diversity, and composed of small‐sized, low‐tiered suspension‐feeding opportunists. Epifaunal communities increased in complexity and tiering after ∼1 million years as crinoids and bryozoans returned. Complexity and depth of burrowing communities only returned to pre‐crisis levels by the Middle Triassic.

Key Concepts:

Tiering is considered as a proxy for the ecological complexity of ancient communities.

Late Palaeozoic reefs and mud mounds bore complex substrate topographies produced in part by microbial carbonate production: these supported diverse and well‐tiered open and cryptic communities that persisted to the end of the Permian.

Infaunal tiering developed slowly from the Ordovician, with occupation of deeper depths being achieved only by the Lower Carboniferous.

Post‐Permian mass extinction epibenthic and infaunal biotas consisted of very low diversity, small‐sized and low‐tiered communities.

Epifaunal communities increased in complexity and tiering as crinoids and bryozoans returned. Infaunal communities saw the return of suspension feeders and finally crustaceans, but the size and depth of burrowing communities only returned to pre‐crisis levels by the Middle Triassic.
Population Genetics: Overview
Authors: Ewens Warren J
Published: September 2010

Population genetics is concerned with the nature of, and the forces determining, the genetic composition of a population. Since any presently observed population is the outcome of an evolutionary process, the subject is in large part concerned with evolutionary questions. Indeed the evolutionary component of population genetics may be thought of as the rewriting of the Darwinian theory in terms of the Mendelian hereditary mechanism. This involves, for example, determining the rate of incorporation of favourable new alleles into a population, and the evolutionary effects of mutation. These activities are
prospective
, that is they discuss changes in the structure of a population forwards in time. However population genetics theory is currently largely
retrospective
, assessing the past history of a population (‘When and where did the most recent common ancestor of all currently living humans live?’) and investigating what forces led to the currently observed genetic composition of a population.

Key Concepts:

The
additive genetic variance
is that component of the variation in any character which is explained by ‘genes within genotypes’.

The
blending theory
asserts that the value of any characteristic of any child is approximately the average of the corresponding characteristics in that child's parents.

The
correlation between relatives
is the correlation in some character between close relatives (e.g. mother–daughter).

The
Fundamental Theorem of Natural Selection
relates aspects of the change in the mean fitness of a population from one generation to the next to the parental generation additive genetic variance in fitness.

The
Hardy–Weinberg law
shows that, in the absence of selection, genetic variation is maintained from one generation to the next.

The
neutral theory
claim that most of presently observed genetic variation in a population, and most of the variation from one population to another, did not arise as a result of selection but arose rather as a result of purely random changes in allelic frequencies.

Retrospective population genetics theory
focuses on the past history of a population rather than its future evolution.
Seed Banks and Gene Banks
Authors: Ambrose Michael J
Published: September 2010

The doomsday seed vault buried deep in the side of a frozen mountain‐side on the Island of Svalbard situated within the Arctic Circle has come to encapsulate the global imperative of conserving the biodiversity relating to the world's major food crops against the growing challenges resulting from rising human population, lost of agricultural land and climate change. Extending seed longevity in seed and gene banks is regarded as complementary to conserving plant genotypes

in situ

in their natural environment. Elucidating the basis and variation in seed physiology with respect to seed storage as well as other

in vitro

storage techniques such as cryopreservation are essential to success in this mission and in enabling ready access to these resources for future generations.

Key Concepts:

Crop wild relatives are wild plant taxa that are closely related to a crop such as a wild ancestor, from which it might be possible to find and transfer beneficial traits for crop improvement.

The classification of survival of species on the basis of the response of seeds to combinations of temperature and desiccation.

Genetic resources is the term that refers to any material that contains functional units of heredity.

Seeds with intermediate storage behaviour can tolerate moderate desiccation (8–12% moisture) but are sensitive to dry storage at temperatures at or below freezing.

Serotiny is an ecological adaptation whereby some plant species release their seeds in response to environmental cues such as wetting, burning or warmth rather than the time when the seed reaches maturity.

Seeds can be subjected to accelerated aging by storing seeds for short periods under stressed conditions of high humidity and high temperatures. This results in a fall in percentage germination that mimics the effect observed under long‐term storage.
Protein Import into the Yeast Endoplasmic Reticulum: Methods
Authors: Brodsky Jeffrey L , Morrow Michael W
Published: September 2010

Nascent secreted proteins and integral membrane proteins in eukaryotes must be imported, or ‘translocated’ into the endoplasmic reticulum (ER). Because approximately one‐third of all cellular proteins fall into these protein classes, the translocation machinery in the ER must operate with high efficiency and accommodate a wide variety of chemically diverse substrates. Moreover, proteins can translocate into the ER either cotranslationally or posttranslationally, and each of these modes of protein entry into the ER requires unique components. Through the years, the composition and function of the ER translocation machinery was defined by the development of

in vitro

assays in which protein translocation can be recapitulated. For example, the posttranslational translocation of a model protein into the yeast ER can be measured using ER‐derived microsomes or reconstituted proteoliposomes. The model protein for this assay is the mating pheromone precursor, prepro‐alpha factor.

Key Concepts:

A large number and variety of proteins must be imported, or ‘translocated’ into the ER.

Proteins can enter the ER either cotranslationally, that is during synthesis, or posttranslationally, that is after synthesis.

The translocation reaction requires a multiprotein complex and associated factors which reside in the cytoplasm, in the ER membrane and in the ER lumenal space.

Posttranslational translocation can be recapitulated using ER‐derived microsomes prepared from the yeast
Saccharomyces cerevisiae
, or using reconstituted proteoliposomes into which the translocation machinery has been integrated.

The
in vitro
reaction has helped to define how components of the translocation machinery function.

The translocated substrate can be mutated to assess how aberrant proteins are targeted for ER‐associated degradation (also known as ERAD).
Fourier Transform Infrared (
FTIR
) Spectroscopy
Authors: Gerwert Klaus , Kötting Carsten
Published: September 2010

Fourier transform infrared (FTIR) spectroscopy is an experimental technique used initially for qualitative and quantitative analysis of organic compounds, providing specific information on molecular structure, chemical bonding and molecular environment. For many years, FTIR has been successfully employed for studying a wide variety of proteins, enzymes, nucleic acids, lipids and glycolipids and photobiological systems. Time‐resolved (tr)‐FTIR spectroscopy can monitor reactions of the amino acids, the ligands and specific water molecules in the active centre of a protein in the time range from nanoseconds to seconds, thereby providing a detailed understanding of the molecular reaction mechanism.

Key Concepts:

FTIR provides several advantages compared to other spectroscopic techniques.

FTIR spectroscopy is widely used for the investigation of secondary protein structure.

To obtain information on individual groups, we have to look at difference spectra.

In order to derive information on the reaction mechanism, the infrared bands have to be assigned to molecular groups of the protein.

The QM/MM (quantum mechanics/molecular mechanics) approach can be used to calculate the infrared spectra of proteins.

With the ATR (attenuated total reflection) technique it is possible to immobilise a protein on a surface and study reactions with ligands or other proteins.

Biochemical changes of tissues and body fluids can be monitored using FTIR.

By means of infrared microscopes spatial resolved information with a resolution of a few micrometer can be obtained.
Chemical Ecology
Authors: Drijfhout Falko
Published: September 2010

Chemical ecology is the study of the structure, origin and function of naturally occurring chemicals that mediate intraspecific or interspecific interactions. These chemicals are known as semiochemicals. Depending on the function of a semiochemical, this group of chemicals can be further divided into three classes: pheromones, kairomones and allomones. At the heart of the discipline are modern analytical instrumentation, careful observational biology and good bioassay design. Research during the past 50 years has identified many different semiochemicals. Several of these chemicals are currently in use as pest control agents. Although the majority of the early research focused on (lepidopteran) sex pheromones, in recent years, a shift is seen into semiochemicals from other insects as well as noninsects such as mammals, marine animals or even micro‐organisms. The field of chemical ecology has developed into a mature science with diverse practical applications, of which pest control is the most important.

Key Concepts:

Chemical ecology studies the structure, origin and function of naturally occurring chemicals that mediate intraspecific or interspecific interactions.

Bioassays are crucial in successfully identifying active semiochemicals.

Semiochemicals are divided into different categories, depending on their function in an organism.

Chemical ecology has a much wider application than only its use in pest control.

Chemical ecology is characterised by highly cross‐disciplinary research.
Cancer: Chromosomal Abnormalities
Authors: Mitelman Felix
Published: September 2010

Most cancer cells have acquired clonal chromosome abnormalities. An increasing number of characteristic aberrations, in particular balanced changes, are with remarkable specificity associated with distinctive morphological and clinical disease characteristics. The identification of these recurrent aberrations has several important implications. First, cytogenetics has become an increasingly important tool in the clinical management of cancer patients to help establish a correct diagnosis, to predict prognosis, and to select the most appropriate treatment. Second, the cytogenetic information has provided invaluable help to identify genes of importance in the carcinogenic process by focusing the attention to chromosomal sites that may harbour genes which when rearranged lead to neoplasia. Practically all balanced structural rearrangements that have been characterised at the molecular level have been found to exert their action through one of the two alternative mechanisms: deregulation, usually over‐expression, of a seemingly normal gene in one of the breakpoints, or the creation of an abnormal hybrid gene through fusion of parts of two genes, one in each breakpoint.

Key Concepts:

Chromosome aberrations are a characteristic feature of neoplasia.

Chromosome abnormalities have been reported in almost 60 000 human neoplasms.

Recurrent balanced chromosome rearrangements, in particular translocations, are associated with distinctive tumour characteristics.

Cancer‐associated chromosome changes are of clinical importance for diagnosis, prognosis and treatment.

The breakpoints of balanced structural chromosome aberrations point at the locations of cancer‐relevant genes.

Cancer‐associated structural chromosome abnormalities lead to the formation of hybrid genes through fusions of parts of two genes located in the breakpoints.

More than 600 gene fusions created by an acquired chromosome change are known, and about 30% of human cancer cases contain a fusion gene.
Meiosis
Authors: Hultén Maj A
Published: September 2010

Meiosis is a specialised type of cell division, the principal function of which is to produce spores/gametes (sperm and eggs in mammals) that have the haploid number of chromosomes. In humans, this represents a reduction from 46 (23 pairs) to 23 chromosomes (one complete set) in sperm and eggs. The normal somatic number of 46 chromosomes is restored at fertilisation. The most complex part of meiosis (prophase I) involves intimate pairing and synapsis of the homologous chromosomes followed by reciprocal recombination/crossing‐over/chiasma formation. In most organisms, chiasma formation is obligatory to allow the regular segregation of the (rearranged) homologues at the first (reductional) division (anaphase I). In mammals, there are substantial differences between the two sexes as regards the meiotic process. Mammalian female prophase I takes place during foetal development, and the second meiotic cell division is not completed until after fertilisation. In sharp contrast, mammalian male meiosis does not start until puberty and is continuous throughout life.

Key Concepts:

Meiosis is the term used for the cell divisions leading to gametes, sperm and eggs in mammals.

At meiosis, the chromosome number is halved compared to that in somatic cell nuclei.

Meiosis takes place in the germ line, testes and ovaries in mammals.

The meiotic process is very different in the two mammalian sexes.

Female mammalian meiosis is subdivided into three stages: the first taking place during foetal development, the second just before ovulation and the third after fertilisation.

Male mammalian meiosis starts at puberty and is ongoing throughout life.

Reciprocal recombination/crossing‐over/chiasma formation (taking place during foetal development in mammalian females) is necessary for normal first meiotic cell division (taking place just before ovulation in mammalian females).

Many of the proteins involved in the meiotic recombination process, as well as some structural components of meiotic chromosomes, are conserved from yeast to man.

Human females produce only 300–400 mature eggs in a lifetime, in stark contrast to human males who normally produce around 300–400 million sperm daily.

An abnormal chromosome number (aneuploidy) is common in humans and is thought to arise due to abnormalities in meiotic cell divisions.
Glucose‐6‐phosphate Dehydrogenase (G6PD) Deficiency: Genetics
Authors: Mason Philip J , Vulliamy Thomas J
Published: September 2010

Deficiency ofglucose‐6‐phosphate dehydrogenase(G6PD) is the most common enzyme deficiency in humans and is due to many different local variants with point mutations in the X‐linked G6PD gene. In populations that have a history of malaria infection G6PD alleles causing deficiency can reach frequencies of 10% or more. Though often asymptomatic, the enzyme deficiency can lead to acute haemolytic anaemia caused by failure to maintain sufficiently high levels of nicotinamide–adenine dinucleotide phosphate reduced form (NADPH) to prevent oxidative damage in red cells. Rare sporadic variants that can occur in all human populations can cause more severe chronic haemolytic anaemia. G6PD deficiency is also one of the major causes of neonatal jaundice. The prevalence of G6PD‐deficient alleles is likely due to the fact that they confer a selective advantage against malaria infection.

Key Concepts:

G6PD deficiency is widespread because deficient individuals have a selective advantage against malaria infection.

G6PD in red cells maintains the levels of NADPH, essential for reducing oxidising agents.

Deficient variants cannot maintain high NADPH levels and reactive oxygen species cause haemolysis.

Deficient variants can reach polymorphic levels and different populations have different variants.

This pattern of variation arose recently, coincident with the spread of malaria in human populations.

Most deficient variants are unstablein vivoand therefore cause very low levels in red cells, where the enzyme is not turned over.

Knowledge of the G6PD variants in a population can be useful in limiting illness caused by G6PD deficiency.
Macrophage Foam Cells
Authors: Valledor Annabel F , Lloberas Jorge , Celada Antonio
Published: September 2010

Foam cells are lipid‐loaded macrophages that are generated from the massive uptake of modified low‐density lipoproteins and the intracytoplasmatic accumulation of cholesteryl esters. Foam cells are present in all stages of atherosclerosis and participate in inflammatory responses and tissue remodelling within the arterial intima. Foam cells can also be generated as a consequence of infection by persistent pathogens, such as

Mycobacterium

,

Chlamydia

and

Toxoplasma

. These pathogens meet nutritional advantages by residing within cells that accumulate lipids. When the immune system is unable to eliminate substances perceived as foreign, it produces a granuloma, composed mostly of macrophages, attempting to wall off the nonself‐material. This article reviews the processes that lead to the regulation of foam cell formation in atherosclerosis and infection.

Key Concepts:

Foam cells are lipid‐loaded macrophages.

Foam cells are generated from the massive uptake of modified low‐density lipoproteins and the intracytoplasmatic accumulation of cholesteryl esters.

Foam cells are present in several diseases as atherosclerosis and as result of different infections.

Foam cells participate in inflammatory responses and tissue remodelling.

Endothelial transmigration of monocytes is the first step in the development of atherosclerosis.

Once monocytes have taken residence in the arterial wall intima, they undergo phenotypic transformation into macrophages, and can internalise large amounts of modified LDLs and become foam cells.

Liver X receptors (LXR) and the retinoid X receptors (RXR) heterodimers directly upregulate the expression of a number of genes involved in lipid and lipoprotein homeostasis.

When the immune system is unable to eliminate substances that it perceives as foreign it attempts to wall off the nonself‐material by producing granulomas; a ball‐like structures composed of immune cells, mostly activated macrophages, that are surrounded by lymphocytes predomintantly of the T
H
1 type.
Heliobacteria
Authors: Asao Marie , Madigan Michael T
Published: September 2010

Heliobacteria are the most recently discovered of the anoxygenic phototrophic bacteria. Heliobacteria contain bacteriochlorophyllg, a pigment unique to species of this group, and synthesise the simplest photosynthetic complexes of all known phototrophs. Also, unlike all other phototrophs, heliobacteria produce endospores but cannot grow autotrophically. Four genera of heliobacteria are known. Species ofHeliobacterium,HeliobacillusandHeliophilumgrow best at neutral pH, whereas species ofHeliorestisare alkaliphilic.Heliobacterium,HeliobacillusandHeliophilumspecies form one phylogenetic clade whereasHeliorestisspecies form a second within the phylum Firmicutes of the domain Bacteria. Heliobacteria have a unique ecology, being primarily terrestrial rather than aquatic, and some species may have evolved a mutualistic relationship with rice plants. The genome sequence of the thermophileHeliobacterium modesticaldumsupports the hypothesis that heliobacteria are minimalist phototrophs, and because of this, heliobacteria may have played a pivotal role in the evolution of phototrophic bacteria.

Key Concepts:

Heliobacteria are unlike all known anoxygenic phototrophic bacteria because of their unique bacteriochlorophyll, Gram‐positive phylogeny, and primarily soil habitat.

Heliobacteria employ the simplest of all photosynthetic energy‐generating systems and thus their study may yield important clues to when and how photosynthesis evolved.

In addition to being phototrophic, heliobacteria are strong nitrogen‐fixing bacteria and possibly associate with plants such as rice in a type of symbiotic association.
Apoptosis in Developmental Processes
Authors: Entezari Maria , Zakeri Zahra , Lockshin Richard A
Published: September 2010

Embryonic development and differentiation to adult form depends on orchestration of cell division and death. In embryos, programmed death sculpts form, opens lumens, separates or splits tissue layers, allows tissue layers to fuse and removes vestigial organs. Both the central nervous and immune system overproduce cells and destroy those that do not form successful synapses or produce unusable antibodies. Cell death is first seen in mammalian embryos when the blastocyst expands, but elsewhere, the first deaths are not seen before the maternal‐zygotic transition. Abnormal timing, amount or localisation of cell death leads to abnormalities or death of embryos.

Several signalling pathways trigger cell death. Usually the signals activate caspases (first discovered in embryonic cell death in nematodes) and lead to apoptosis, although apoptosis is not the only form of cell death. The signalling mechanisms that control cell death in embryos are not well understood, but should be if we hope to understand normal and teratological development.

Key Concepts:

Cell death can be seen in both embryonic development and normal growth of adult tissue.

The embryonic cell deaths are highly programmed in that they are predictable in location, time and amount. In the simplest instances, such as in nematodes, control of cell death is under direct control of a small number of genes.

Most but not all of the embryonic deaths are apoptotic.

Embryonic cell to sculpt the embryo and define the boundaries of tissues and organs. In the central nervous system and the immune system, overgrowth (production of excessive cells) and subsequent pruning by cell death generate the high specificity that characterises these systems.

Deregulation of apoptosis can produce many embryonic abnormalities and teratologies and, later in life, produces cancers, autoimmune disease or neurodegenerative disease.

There are many means to study cell death, but only a few are directly applicable to the study of cell death in embryos. Nevertheless, further study is needed to understand the signalling mechanisms that decide the death of cells in specific locations and times.

Learning more about cell death in embryos will help us to understand how it is controlled in adults.
Neuroscience of Autism
Authors: Blatt Gene J
Published: September 2010

Autism is a pervasive developmental disorder characterised by abnormal social–emotional behaviours, repetitive or stereotyped behaviours and delayed or impaired development of language skills. Neuropathological studies have revealed that multiple brain areas are affected in the disorder including the limbic system (hippocampus, amygdala and cingulate cortex), cerebellum, brain stem (inferior olivary nucleus) and parts of the cerebral cortex. There is a decrease in the number of cerebellar Purkinje cells in many individuals with autism. The cerebellum normally functions as an error correction system for fine motor behaviours and has also been implicated in cognitive behaviours. Over the past decade, research has focused on two transmitter systems, serotonin and γ‐aminobutyric acid (GABA). It has been reported that specific types of enzymes and receptors are deficient in individuals with autism. Despite these research findings, effective pharmacotherapies have not yet been developed and treatment outcomes vary.

Key Concepts:

Autism is characterised by deficits in social–emotional behaviour, stereotyped or repetitive behaviours and delayed/impaired development of language.

Many individuals with autism have decreased numbers of cerebellar Purkinje cells.

Neuropathology findings indicate that changes in the brain begin in prenatal development and extend into the postnatal period.

Brain overgrowth occurs during the early postnatal period especially in the frontal lobe region in individuals with autism suggesting abnormal connectivity.

Consistent results from postmortem studies indicate that in the central nervous system, the inhibitory GABA neurotransmitter system is involved in the disorder.

Specific types of GABA, serotonin, acetylcholine and glutamate neurotransmitter receptors appear to be affected in the disorder.

Imaging studies have demonstrated that in some brain areas in autistic individuals, differential activation patterns within a particular structure and in laterality.

Research efforts are continuing to report interesting findings but no cure or consistent effective treatments have been found.
Role of Polymorphisms in Cancer Susceptibility
Authors: Tan Iain Beehuat , Ngeow Joanne , Tan Patrick
Published: September 2010

Genetic variations or polymorphisms existing in the human genome can confer genetic susceptibility to cancer. Rare early onset cancer predisposition syndromes such as Li‐Fraumeni and Cowden syndromes typically involve germline mutations exhibiting high‐penetrance effects, but these account for only a small proportion of human cancers. For sporadic cancers, early monogenic association studies focusing on candidate genes with strong biological hypothesis have demonstrated an increased risk of cancers associated with polymorphisms in genes involved in cell cycle control, carcinogen metabolism, DNA (deoxyribonucleic acid) repair, apoptosis, inflammation and epigenetic regulation. Recent genome‐wide association studies have gone beyond the monogenic candidate gene approach to search across the entire genome for cancer susceptibility loci. This exponential knowledge has increased our understanding of carcinogenesis and provided translational research opportunities into personalised risk assessment, therapy and drug discovery.

Key Concepts:

Rare hereditary cancer syndromes such as Li‐Fraumeni syndrome typically involve high‐penetrance mutations of oncogenes or tumour suppressor genes, but account for a minority of human cancers.

The overwhelming majority of cancer susceptibility in the normal population is likely attributable to common genetic variations or polymorphisms in the human genome.

Candidate gene approaches have identified several polymorphisms of known oncogenes and tumour suppressor genes, as well as genes involved in carcinogen metabolism, DNA repair and cell‐cycle control that are associated with cancer susceptibility.

The increased risk conferred by each polymorphism is small.

Data from separate association studies are often conflicting. Meta‐analysis can be used to integrate conflicting findings across several studies.

The functional mechanisms by which many polymorphisms lead to cancer susceptibility has not been established.

In recent years, high‐resolution public databases of genetic information, technological advances and reduced costs of genotyping have led to a rapid emergence of genome‐wide association studies (GWAS) that survey the entire genome for cancer susceptibility loci.

By these approaches, putative risk loci, novel cancer genes have increased biological insights into carcinogenesis.

This exponential increase in knowledge has opened new horizons to understand oncogenesis and translational research opportunities into personalised risk assessment, therapy and drug discovery.
Molecular Genetics of Emery–Dreifuss Muscular Dystrophy
Authors: Morris Glenn E , Sewry Caroline A , Wehnert Manfred
Published: September 2010

Emery–Dreifuss muscular dystrophy (EDMD) is a rare neuromuscular disorder typically characterised by early contractures, slowly progressive muscular wasting, and life‐threatening heart conduction disturbances, which can develop into a cardiomyopathy. Some severe neonatal cases have also been identified. There is a wide intrafamilial and interfamilial clinical variability. Genetically, X‐linked recessive (
EMD1
and
EDMD6
), autosomal dominant (
EMD2
,
EDMD4
and
EDMD5
) and autosomal recessive (EMD3) forms can be distinguished. By molecular genetic methods, EDMD can be associated with mutations in the

STA

(emerin gene symbol),

LMNA

(lamin A/C gene symbol),

SYNE

(nesprin gene symbol)
1
,

SYNE2

and Four and a Half LIM Domain 1 (

FHL1

) genes. Female carriers of the X‐linked forms may manifest with cardiac symptoms but heterozygous carriers of the autosomal forms do not show symptoms. Only approximately 46% of unrelated EDMD patients have a mutation in known genes pointing to further genetic heterogeneity in EDMD. The molecular pathogenesis is unresolved, but there is evidence for gene expression changes via altered nuclear signalling and for reduced resistance of muscles to physical damage during contraction.

Key Concepts:

Emery–Dreifuss muscular dystrophy (EDMD) is a neuromuscular disorder recognised clinically by three features: early contractures, a characteristic pattern of muscle wasting and cardiac conduction defects.

EDMD was originally described as an X‐linked disorder, later found to be caused by mutations in the
STA
gene encoding a nuclear membrane protein, emerin.

Molecular genetic analysis allows precise subtyping of EDMD into X‐linked forms (
STA
and
FHL1
associated), autosomal dominant forms (
LMNA
,
SYNE1/SYNE2
associated) and an autosomal recessive form (
LMNA
associated).

Wide clinical variability of EDMD and clinical overlap with other clinical entities frequently require consideration of patients not completely fulfilling the EDMD diagnostic criteria for molecular genetic differentiation in
STA
,
LMNA
,
SYNE1/SYNE2
and
FHL1
.

Digenic pathogenesis has been observed including
LMNA
/
STA
,
LMNA
/
DES
and
SYNE1/SYNE2
.

In most cases, EDMD mutations affect proteins located in the nuclear membrane where they interact with each other.

Many patients do not have mutations in genes identified so far, so further genes are expected to be involved in the pathogenesis of EDMD.
Molecular Genetics of Multiple Myeloma
Authors: Bi CL , Chng WJ
Published: September 2010

Multiple myeloma (MM) is the second most common haematologic malignancy causing significant mortality and morbidity. The initial malignant clone undergoes multistep transformation, which could results from genetic and epigenetic deregulation, the acquisition of clonogenic properties and also abnormal interaction with tumour microenvironment. Two patterns of primary genetic events have been described: recurrent translocations involving the immunoglobulin heavy chain (IgH) locus and hyperdiploid characterised by chromosomal trisomies. Besides playing an important role in disease pathogenesis, these genetic abnormalities also have important prognostic impact. Further, the genes and pathways dysregulated in high‐risk disease can be used to develop specific therapeutic strategies. In this article, we concentrate on molecular pathways deregulated by genetic and epigenetic abnormalities, and their potential biological and clinical implications.

Key Concepts:

All multiple myeloma have a preceeding premalignant monoclonal gammopathy of undetermined significance phase.

Two dichotomous pathways are involved in disease initiation: translocations involving the immunoglobulin heavy chain and hyperdiploidy involving recurrent trisomies in chromosomes 3, 5, 7, 9, 11, 15 and 19.

All primary disease‐causing events lead to universal overexpression of one or more cyclin D gene.

MYC activation or reduction of retinoblastoma gene functions may be involved in disease transformation.

Additional mutations affecting the nuclear factor kappaB and p53 pathways may lead to independence from stromal environment leading to disease progression.

Genetic abnormalities are powerful prognostic factors in myeloma and can be used to define patients with high‐risk disease.

Certain novel therapeutic agents can overcome the poor prognosis of cytogenetics. As such, risk stratification in the treatment of myeloma is a possibility.
Haplotype Sharing Methods
Authors: Beckmann Lars
Published: September 2010

A convenient way to incorporate haplotypes into statistical analysis of complex diseases is the use of haplotype sharing measures. Statistical methods summarise evolutionary events such as mutation, recombination and coalescence into simple scores to improve the power of association tests. Existing methods provide flexible tools for various study designs such as pedigree data and case‐control data, in candidate gene analysis and for genome‐wide association analysis. Although haplotype sharing methods were powerful in detecting disease mutations in isolated populations, their applicability for complex diseases in general population deserves further investigation as their potential for possible extensions using a variety of genomic variants, such as copy number variation and uncommon sequence mutations.

Key Concepts:

Statistical methods for haplotype sharing analysis in candidate gene association analysis and genome‐wide studies have been developed that incorporate information of local haplotypes to improve the power to identify disease susceptibility variants.

Haplotype sharing analysis of complex disease relies on population genetic assumptions and incorporates in a convenient way of mutations and recombinations.

Statistical methods based on haplotype sharing are available for various study designs, types of trait variable and genetic and nongenetic data.

Haplotype sharing analysis extends the identical by descent concept, successfully applied in linkage analysis, to population‐based association studies.

Reducing a potentially large number of haplotypes to simple similarity scores may reduce degrees of freedom for hypothesis testing, and thus may improve the power.

Haplotypes with low frequencies can easily be considered.

Haplotype sharing analysis may be more powerful than conventional methods in detecting rare variants.
Horizontal Gene Transfer in Evolution
Authors: Boto Luis
Published: September 2010

Twenty years ago the concept of horizontal or lateral gene transfer (the nongenealogical transmission of genetic material between organisms) was introduced as an explanation to incongruence in phylogenetic reconstructions using different genes. Today, horizontal gene transfer is accepted as an important force modulating evolution of prokaryotes and unicellular eukaryotes, whereas the extent to which it impacts on the evolution of metazoan eukaryotes remains unknown. Evidence for the role of horizontal gene transfer in evolution put in question the metaphor of the tree of life and the traditional view of evolution as a slow process. A more pluralistic approach to evolution is emerging that encompasses different evolutionary mechanisms operating at different levels of complexity.

Key Concepts:

Horizontal gene transfer is the nongenealogical transmission of genetic material between different organisms.

Horizontal gene transfer plays an important role in prokaryotic evolution.

Horizontal gene transfer also modulates evolution of unicellular eukaryotes.

The importance of horizontal gene transfer in metazoan evolution is uncertain.

Horizontal gene transfer challenges the tree of life metaphor.

Horizontal gene transfer challenges the traditional view of evolution as a slow process.

A pluralistic approach to evolution is needed.
Molecular Evolution of Glycophorins
Authors: Wilder Jason A
Published: September 2010

Humans and closely related apes have four glycophorin‐encoding genes, three of which form a small paralogous gene family. These genes encodesialoglycoproteinsthat localise to the plasma membrane of the red blood cell. Although the biological function of these proteins is not well understood, and their presence does not appear necessary for human viability or normal health, all four glycophorin‐encoding genes show evidence of accelerated evolution through positive natural selection. This selection is likely caused by a coevolutionary dynamic between glycophorins andPlasmodium falciparumreceptors that use these molecules to gain entry into the red blood cell.

Key Concepts:

Gene duplication, followed by DNA sequence divergence and non‐homologous recombination, has shaped theGYPA‐GYPB‐GYPCgene family.

Positive natural selection, likely mediated byPlasmodium falciparum, has caused accelerated amino acid evolution at all glycophorin‐encoding genes.
Evolution of Plant Homeobox Genes
Authors: Mukherjee Krishanu , Brocchieri Luciano
Published: September 2010

Plant homeobox genes can be classified into 14 evolutionary classes, each characterised by fusion of the homeodomain with class‐specific codomains. Among these classes only
BEL
and
KNOX
are found in red algae, whereas unicellular green algae also include members of the classes
WOX
,
DDT
and
PINTOX
. All 14 classes are found only in land plants, including moss and vascular plants, suggesting that homeobox genes have proliferated within each class particularly in flowering plants, indicating that all classes had already differentiated in the common ancestor of moss and vascular plants. In different land plants, including moss and flowering plant, multiple gene copies are observed for most classes, suggesting that proliferation and functional differentiation of gene paralogues within the original classes reflects the increasing complexity of plant development and architecture.

Key Concepts:

Homeobox genes in plant can be classified into 14 distinct classes all of which had appeared in the common ancestor of Bryophyta and Tracheophyta.

Functional differentiation of plant homeodomain protein classes relates to acquisition of a class‐specific codomain architecture.

Proliferation of paralogous genes within each class in land plants concomitantly with increasing organismal complexity.
Evolution of Eukaryotic
RNA
Polymerases
Authors: Drouin Guy , Carter Robert
Published: September 2010

Ribonucleic acid (RNA) polymerases
are responsible for the transcription of
deoxyribonucleic acid
(DNA) into RNA. The number of protein subunits making up these enzymes has increased during evolution from 5 in Eubacteria to 12 in the common ancestor of Archaea and eukaryotes. Eukaryotes have three
RNA polymerases
, each transcribing a particular subset of genes.
RNA polymerase I
transcribes ribosomal RNA genes,
RNA polymerase II
transcribes messenger RNA genes and
RNA polymerase III
transcribes 5S and transfer RNA genes. Although
RNA polymerase II
is still made up of 12 subunits, the number of subunits has increased to 14 in
RNA polymerase I
and to 17 in
RNA polymerase III
. These new subunits originated from the permanent recruitment of pre‐existing general transcription factors. Interestingly, the evolution of the three eukaryotic
RNA polymerases
has been affected not only by adaptive forces but also by the nonadaptive forces due to the concerted evolution of the genes they transcribe.

Key Concepts:

The larger numbers of protein subunits found in RNA polymerases I and III, relative to RNA polymerase II, are due to the permanent recruitment of general transcription factors.

The three universal eukaryotic RNA polymerases have specific functional differences near their respective active sites.

During evolution, the three eukaryotic RNA polymerase have been selected to better perform their specific tasks.

The rate of evolution of RNA polymerases is proportional to the amount of homogenisation (concerted evolution) experienced by the genes they transcribe.

Nonadaptive processes therefore also affect the rate of evolution of RNA polymerase genes.
Evolution of the Interferon Regulatory Factor Family
Authors: Nehyba Jiří , Hrdličková Radmila , Bose Henry R
Published: September 2010

The interferon regulatory factors (IRFs) are a family of transcription factors that play central roles in immune defence and stress responses. All IRF proteins share a
deoxyribonucleic acid
(DNA)‐binding domain. IRF genes first appeared in the last common metazoan ancestor. In sponges, placozoans and ctenophores the number and diversity of the IRF family are limited. In cnidarians and bilaterians, the IRF genes diversified into the
IRF1
and
IRF4
branches. The IRF family, especially the
IRF4
genes, expanded several times in distinct groups of bilaterians to include as many as 14 family members. In nematodes and insects, IRF genes were eliminated or mutated beyond recognition. The 10 vertebrate IRF genes arose by the 2‐fold whole genome duplication in early vertebrates. Repetitive expansions, diversifications or contractions of IRF family suggest the changing selection pressure in the evolution of the metazoan defence systems.

Key Concepts:

The interferon regulatory factors are a family of transcription factors that function as major regulators of host defence in vertebrates.

IRF genes first appeared in the last common metazoan ancestor.

IRF genes are present in all five basal groups of metazoans: sponges, placozoans, comb jellies, cnidarians and bilaterians.

IRF genes have two evolutionary conserved domains, the DNA‐binding domain and the IRF association domain and both are already present in ancient sponges.

In cnidarians and bilaterians, the IRF genes diversified into the IRF1 and IRF4 branches.

The IRF family expanded several times in distinct groups of bilaterians (molluscs, cephalochordates, tunicates and vertebrates).

IRF genes were eliminated or mutated beyond recognition in nematodes and insects.

The 10 members of the vertebrate IRF family originated in early vertebrates as a result of 2‐fold genome duplication.

Some IRF genes were eliminated in certain vertebrate species, whereas additional IRF family members were detected in fishes.

Although the function of the IRF family in vertebrates has been studied in considerable detail, very little is known about the functions of invertebrate IRF genes.
Origin and Genetic Diversity of Pig Breeds
Authors: Amills Marcel , Clop Alex , Ramírez Oscar , Pérez‐Enciso Miguel
Published: September 2010

Genetic and archaeological findings suggest that pig domestication began about 9000–10 000 YBP at multiple sites across Eurasia, followed by their subsequent spread at a worldwide scale. Development of local types throughout the centuries led to the foundation, mostly during the nineteenth century, of current modern breeds with defined phenotypes and production abilities. Extensive intercrossing markedly increased the gene pool of these founder populations. For instance, it is well known that many European pig breeds carry Far Eastern haplotypes at high frequencies because of an ancient introgression with Chinese swine. Since then, artificial selection, genetic bottlenecks and inbreeding have significantly modified the allelic diversity of pig breeds. In the next future, state‐of‐the‐art scientific advances as well as conservation programmes will be fundamental to preserve the genetic reservoir of pig breeds as well as to exploit it in the context of artificial selection schemes.

Key Concepts:

Pigs were domesticated at multiple locations across Eurasia.

Exploratory and commercial journeys favoured the dissemination of European and Far Eastern pigs into Africa and America.

England, United States and China were the main centres of breed development during the eighteenth to nineteenth centuries.

Genetic variation of pigs has been shaped by the complex interplay of artificial selection, population admixture, inbreeding and genetic drift.

Artificial selection is evolution but an accelerated pace; therefore, by comparing breeds that have undergone distinct selective pressures we can glimpse the molecular basis of adaptation.

Approximately 20% of local pig breeds face extinction because of dramatic decreases in their census or extensive intercrossing with foreign populations.

New genotyping and sequencing technologies will revolutionise knowledge on patterns of diversity in livestock species, including pigs.
Genetics of Retinal Disease
Authors: Francis Peter J
Published: September 2010

The retina forms the inner lining of the posterior segment of the eye. Vision is dependent on intact retinal photoreceptors to transduce incident light to an electrical signal for relay to the brain. The function of these cells is in turn reliant upon their intimate relationship with the adjacent retinal pigment epithelium (RPE). Indeed, if RPE cells become degenerate or are lost, PR degeneration ensues and

vice versa

. These events form the basis of vision loss in many retinal degenerative diseases and are key features of such conditions as age‐related macular degeneration (AMD), retinitis pigmentosa and other genetically inherited retinal diseases such as Stargardt macular dystrophy. Cumulatively, these conditions now comprise the foremost causes of untreatable visual loss in developed countries. The diverse phenotypes observed reflect the remarkable genetic heterogeneity of retinal disease. Furthermore, different mutations within the same gene can cause different phenotypes. AMD is now known to be a complex genetic disorder with a number of genetic variants (single nucleotide polymorphisms, SNPs) now known to confer susceptibility to vision loss from the condition.

Key Concepts:

The retina is a multilayered neural tissue that comprises a variety of highly specialised cells that receive and process visual stimuli.

The majority of genetic diseases of the retina affect the photoreceptor cell.

Although many diseases affect the whole retina, certain conditions affect predominantly or exclusively the macula of the eye, that region of the retina specialised for central vision.

More than 200 genes have been identified that cause monogenic retinal degeneration in humans.

Hundreds of mutations have been described that can be inherited as autosomal dominant, recessive, X‐linked, mitochondrial, oligogenic and digenic traits.

Monogenic retinal diseases are slowly progressive and in many instances lead to blindness.

Age‐related macular degeneration is the most frequent cause of blindness in older individuals. It is a complex disease, one that arises due to the interplay of both multiple genetic and environmental factors.

Although major advances are being made in treating these with gene and stem cell therapies, there is no currently approved treatment.