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This chapter reviews the major advances in autosomal recessive and autosomal dominant ataxias, discusses the use of genetic tests in these disorders, and summarizes some current ideas regarding pathogenesis. It also presents a list of the autosomal recessive ataxias that have been genotypically characterized to date. Mutations in ataxia with isolated vitamin E deficiency (AVED) are scattered throughout the gene and some of them may be associated with a mild phenotype, late onset, retinitis pigmentosa, and retained reflexes. A syndrome of ataxia associated with optic atrophy, visual loss, and cochlear degeneration has been mapped to chromosome. The spinocerebellar ataxia (SCAs) exhibits many phenotypic similarities so that it is almost impossible to diagnose the genotype from the phenotype alone. Many persons from families with ataxia will request predictive testing and occasionally prenatal testing. Disease-modifying therapies are under investigation and include antioxidants and drugs that may modify excitotoxicity or apoptosis.
Advances in genetics have probably had more practical applications in the field of the inherited neurological disorders than in any other area of medicine. A remarkably high number of serious neurological disorders follow single-gene Mendelian inheritance, in both childhood and adult life. Genetic testing now forms an important and integral part of both neurological and clinical genetics practice and has greatly enhanced both diagnostic precision and the options associated with genetic counseling. This chapter focuses on the use and implications of testing, especially in relation to genetic counseling. Risk estimations in relation to carrier testing for both autosomal and X-linked recessive disorders may, in fact, be quite complex and may need the overall family structure to be considered. The chapter also presents some of the numerous issues that need to be considered in relation to presymptomatic testing.
This chapter reviews the epidemiology, clinical phenotype, and genetic basis of the heritable forms of amyotrophic lateral sclerosis (ALS) and other disorders of the lower motor neuron (LMN) including Kennedy's disease, the spinal muscular atrophies (SMA), and hereditary motor neuropathies (HMN). The first successful genome-wide linkage study on FALS described linkage to chromosome 21q21. Mutations were subsequently identified in the gene encoding Cu/Zn superoxide dismutase (SOD1). Many people with sporadic ALS seek genetic counseling once they become aware that ALS can be genetic and are better informed about gene testing. The implications of gene screening should always be discussed in detail with the family prior to testing. Consent and DNA from an affected individual should be obtained before predictive testing in at-risk individuals is considered. The penetrance of different SOD1 mutations in particular varies greatly and must be taken into consideration when ascribing risk to a particular gene carrier.
Alzheimer's disease is the major cause of dementia in the elderly and afflicts about four million Americans. This chapter focuses on AD and discusses other dementias to the extent to which they contribute to our understanding of AD. While AD is easily the most prevalent dementing disease, other rarer dementias offer useful comparators. These include dementia with Lewy bodies (DLB), prion disease, Worster drought syndrome (British dementia), and frontal temporal dementia (FTD) with tangles (FTDP-17T). The genetic findings have enabled the creation of transgenic mice that model parts of the disease process. While Alzheimer patients are undoubtedly better treated than they were 15 years ago, the only direct benefit to patients from this gene-based approach to research, to date, has been the availability of genetic testing in the kindreds with amyloid beta precursor protein gene (APP) and presenilin mutations.
This chapter reviews the major advances in autosomal recessive and autosomal dominant ataxias, discusses the use of genetic tests in these disorders, and summarizes some current ideas regarding pathogenesis. It also presents a list of the autosomal recessive ataxias that have been genotypically characterized to date. Mutations in ataxia with isolated vitamin E deficiency (AVED) are scattered throughout the gene and some of them may be associated with a mild phenotype, late onset, retinitis pigmentosa, and retained reflexes. A syndrome of ataxia associated with optic atrophy, visual loss, and cochlear degeneration has been mapped to chromosome. The spinocerebellar ataxia (SCAs) exhibits many phenotypic similarities so that it is almost impossible to diagnose the genotype from the phenotype alone. Many persons from families with ataxia will request predictive testing and occasionally prenatal testing. Disease-modifying therapies are under investigation and include antioxidants and drugs that may modify excitotoxicity or apoptosis.
Advances in genetics have probably had more practical applications in the field of the inherited neurological disorders than in any other area of medicine. A remarkably high number of serious neurological disorders follow single-gene Mendelian inheritance, in both childhood and adult life. Genetic testing now forms an important and integral part of both neurological and clinical genetics practice and has greatly enhanced both diagnostic precision and the options associated with genetic counseling. This chapter focuses on the use and implications of testing, especially in relation to genetic counseling. Risk estimations in relation to carrier testing for both autosomal and X-linked recessive disorders may, in fact, be quite complex and may need the overall family structure to be considered. The chapter also presents some of the numerous issues that need to be considered in relation to presymptomatic testing.
The future for genetic medicine is bright. Soon we will know much more about human genetic variation, genomic control, and even how we got to the top of the evolutionary tree. The 3.08 billion base pairs (bp) of Homo sapiens DNA have now been sequenced and this ranks with the highest achievements of humans to date. The assignment of a mutation in a gene causing a human disease is the first step in genetic variation. One human disease area for which there is rising hope of early success is the field of pharmacogenetics. The ENCODE project is endeavoring to identify the functional elements in the genome. Advanced draft or complete sequences are now available for five mammals: human, mouse, rat, chimpanzee and dog. Neurogenetics is still in its infancy but it is now part of the core curriculum of most residency training schemes.
The future for genetic medicine is bright. Soon we will know much more about human genetic variation, genomic control, and even how we got to the top of the evolutionary tree. The 3.08 billion base pairs (bp) of Homo sapiens DNA have now been sequenced and this ranks with the highest achievements of humans to date. The assignment of a mutation in a gene causing a human disease is the first step in genetic variation. One human disease area for which there is rising hope of early success is the field of pharmacogenetics. The ENCODE project is endeavoring to identify the functional elements in the genome. Advanced draft or complete sequences are now available for five mammals: human, mouse, rat, chimpanzee and dog. Neurogenetics is still in its infancy but it is now part of the core curriculum of most residency training schemes.
The aim of this study was to evaluate the performance of various boar taint detection methods, measure the relationship between them and identify possible points of improvement for boar taint detection. The methods used to evaluate boar taint in the carcasses of 448 entire male pigs and 17 barrows were the hot iron method (n = 442), a standardised (n = 323) and home (n = 58) consumer meat-evaluation panel, an expert panel assessment of meat and fat (n = 464) and laboratory analysis of skatole, androstenone and indole in fat (n = 464). The axillary odour of a number of slaughtered entire male pigs was also investigated (n = 231). As correlation coefficients were generally weak, a positive result for one of these detection methods did not per se result in a positive result for all other methods. Results of one detection method could not be generalised. The choice to use one or more detection methods deserves consideration depending on the aim of the study. In this paper, we suggest some possible improvements for evaluating boar taint with a consumer panel based on our results and experience. The home consumer evaluation was correlated with the concentration of indole (r = 0.27) but not with skatole or androstenone. We therefore recommend that lab analyses include indole testing. The hot iron method seems to be an easy and fast detection method, which yields comparable or better correlation coefficients with the other detection methods than an expert panel evaluating fat samples. However, the reliability of the hot iron method depends on the training and reliability of one or two assessors. Efforts should be made to further optimise this method by evaluating the effect of testing conditions. The axillary odour score was moderately correlated with the other detection methods (up to 0.32). More research is needed to evaluate the possibilities of axillary odour as a boar taint detection method.
The objective of this study was to investigate the effects of a flaxseed-supplemented diet on archaeal abundance and gene expression of methanogens in the rumen of dairy cows. In all, 11 non-lactating dairy cows were randomly divided into two groups: group A (five cows) and B (six cows). The two diets fed were: (1) the control diet, a conventional dry cow ration; and (2) the flaxseed-supplemented diet, the conventional dry cow ration adjusted with 12.16% ground flaxseed incorporated into the total mixed ration. A cross-over experiment was performed with the two groups of cows fed the two different diets for five 21-day periods, which included the first adaptation period followed by two treatment and two wash out periods. At the end of each feeding period, rumen fluid samples were collected via rumenocentesis and DNA was extracted. Quantitative PCR was utilized to analyze the gene abundance of 16S ribosomal RNA (16S rRNA) targeting the ruminal archaea population and the mcrA gene coding for methyl coenzyme-M reductase subunit A, a terminal enzyme in the methanogenesis pathway. Results demonstrated a 49% reduction of 16S rRNA and 50% reduction of mcrA gene abundances in the rumen of dairy cows fed the flaxseed-supplemented diet in comparison with those fed the control diet. This shows flaxseed supplementation effectively decreases the methanogenic population in the rumen. Future studies will focus on the mechanisms for such reduction in the rumen of dairy cattle, as well as the relationship between methanogenic gene expression and methane production.
The current classification of epileptic seizures, epilepsies, and epilepsy syndromes is considered first. The presence of progressive neurological signs is a cause for concern and suggests a degenerative disorder. Investigations may include biochemical investigation, EEG, video telemetry, cranial imaging, and DNA diagnostics. Affected males with fragile-X have an increased frequency of epilepsy. Estimates of its prevalence vary from 28% to 45%. Seizures may be generalized tonic-clonic, partial with or without secondary generalization, or of multiple types. Advances in human molecular genetic techniques have allowed positional cloning strategies to be applied to identification of the defective genes and their protein products. A number of studies have been performed on the incidence of epilepsy in the offspring of epileptic parents, and provide an empiric risk of 1. 7%-7. 3%, with a median of 4. 2% for all types of seizures, including febrile convulsions and single seizures.
Parkinson's disease (PD) appears as a sporadic disorder in most patients. This chapter discusses the genetics of the Mendelian forms of PD identified to date, focusing on five genes: a-synuclein, parkin, DJ-1, PINK1, and LRRK2 that have been associated conclusively with this disease. Other chromosomal loci including PARK3, PARK10, and PARK11 have been identified by genome-wide approaches, and these regions might harbor further genes for PD. For a few other genes including UCH-L1, NR4A2, SNCAIP, HtrA2/Omi, and GBA there is weaker evidence of association with PD. These loci and genes are also briefly discussed. Emerging data delineate mutations in the LRRK2 gene as the cause of up to 10% of the familial late onset autosomal dominant PD forms, and also of a few sporadic cases. The importance of genetic testing for PD patients is expected to increase in the near future, also raising important ethical issues.
The current classification of epileptic seizures, epilepsies, and epilepsy syndromes is considered first. The presence of progressive neurological signs is a cause for concern and suggests a degenerative disorder. Investigations may include biochemical investigation, EEG, video telemetry, cranial imaging, and DNA diagnostics. Affected males with fragile-X have an increased frequency of epilepsy. Estimates of its prevalence vary from 28% to 45%. Seizures may be generalized tonic-clonic, partial with or without secondary generalization, or of multiple types. Advances in human molecular genetic techniques have allowed positional cloning strategies to be applied to identification of the defective genes and their protein products. A number of studies have been performed on the incidence of epilepsy in the offspring of epileptic parents, and provide an empiric risk of 1. 7%-7. 3%, with a median of 4. 2% for all types of seizures, including febrile convulsions and single seizures.
The human prion diseases have traditionally been classified into Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler syndrome (GSS) and kuru. The clinically defined categories: CJD, GSS, and kuru may be divided further into three etiological categories: sporadic, acquired, and inherited. The coding sequences of mammalian prion protein genes are highly conserved in a similar way to other structural proteins, presumably by deleterious selection of coding mutations. Symptomatic treatment of various neurological and psychiatric features can be provided and a range of supportive services are likely to be required in the later stages of the disease. A number of approaches to rational therapeutics are being studied in experimental models. Anti-PrP antibodies have been shown to block progression of peripheral prion propagation in mouse models, and humanized versions of these antibodies could, in principle, be developed and used for both post-exposure prophylaxis and during established clinical disease.
A flock of 117, 10-month-old Egyptian geese consisting of 90 females and 27 males were utilized in this investigation. Birds were randomly divided into three equal groups, each made up of three replicates of 10 females and 3 males each. The first group was kept under a pasture system (PS) and allowed to swim in water ducts during the daytime (PS) and kept inside the house during the night. The second group of birds were kept in confinement in a house and fed ad libitum on a commercial feed (intensive system (IS)). Birds in the third group (semi-intensive system (SIS)) were released from the house for 6 h a day and given access to the pasture and water ducts. Each group was housed in three pens (replicates) in the SIS. They were given ad libitum access to the commercial feed when in the house. Each pen measured (2 × 3 m2). Natural mating was practiced during the period from November to the end of May. BW of geese under ISS was significantly (P ⩽ 0.05) higher than those under PS and SIS. Egg number, weight and mass of geese in the SIS system were significantly (P ⩽ 0.05) greater than those of geese in the PS and IS systems. Fertility and hatchability percentages were significantly (P ⩽ 0.05) greater in the PS (84.2% and 88.6%) than in the IS (77.5% and 82.8%) and SIS systems (80.7% and 85.5%). Shell weight and thickness were significantly (P ⩽ 0.05) better in the IS and SIS systems than in the PS system. Geese in the PS and SIS systems exhibited significantly higher plasma estradiol-17 and progesterone than those in the IS. Testosterone was significantly higher in IS than in the other systems. Semen quality factor was significantly higher in the PS and SIS systems than in the IS system. Carcass weight was significantly greater in IS and SIS geese than in PS geese, but the PS system resulted in a decreased percentage skin, abdominal fat and liver. Total amount of meat produced per geese was significantly greater in the SIS than in the IS system and greater in the IS than in the PS system.