Medical genetics is a branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics different from human genetics in human genetics is a field of scientific research that may or may not apply to drugs, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders will be considered in human genetics and medical genetics, while diagnosis, management, and counseling of people with genetic disorders will be considered as part of medical genetics.
In contrast, studies of non-medical phenotypes such as eye color genetics will be considered as part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism). Genetic Medicine is a new term for medical genetics and combines areas such as gene therapy, personalized medicine, and rapidly growing new medical specialties, predictive drugs.
Video Medical genetics
Coverage
Medical genetics covers many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinical diagnostic laboratory activities, and research on the causes and inheritance of genetic disorders. Examples of conditions that fall within the scope of medical genetics include birth defects and dysmorphology, mental retardation, autism, mitochondrial disorders, skeletal dysplasia, connective tissue disorders, cancer genetics, teratogens, and prenatal diagnosis. Medical genetics is increasingly becoming relevant with many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances in genetics reveal the etiology for neurologic, endocrine, cardiovascular, pulmonary, ophthalmological, renal, psychiatric, and dermatological conditions.
Sub-specialization
In some ways, many areas of individuals in medical genetics are hybrids between clinical care and research. This is due in part to recent advances in science and technology (for example, looking at the Human genome project) that has enabled an unprecedented understanding of genetic disorders.
Clinical genetics
Clinical Genetics is the practice of clinical medicine with special attention to hereditary disorders. References are made to genetic clinics for various reasons, including birth defects, developmental delays, autism, epilepsy, short stature, and many others. Examples of genetic syndromes often seen in genetic clinics include chromosomal rearrangement, Down syndrome, DiGeorge syndrome (Syndrome Elimination 22q11.2), Fragile X syndrome, Marfan syndrome, Neurofibromatosis, Turner syndrome, and Williams syndrome.
In the United States, clinicians who practice clinical genetics are accredited by the American Board of Medical Genetics and Genomics (ABMGG). To become a certified Clinical Geneticist practitioner, a doctor must complete a minimum of 24 months of training in a program accredited by ABMGG. Individuals seeking admission into clinical genetics training programs should have a M.D. or D.O. Degree (or equivalent) and have completed a minimum of 24 months of training in an ACGME-accredited residency program in internal medicine, pediatrics, obstetrics and gynecology, or other medical specialties.
Metabolic/biochemical genetics
Metabolic (or biochemical) genetics involves the diagnosis and management of congenital metabolic error in which patients have enzymatic deficiencies that interfere with the biochemical pathways involved in carbohydrate, amino, and lipid metabolism. Examples of metabolic disorders include galactosemia, glycogen storage diseases, lysosomal storage disorders, metabolic acidosis, peroxisomal disorders, phenylketonuria, and urea cycle disorders.
Cytogenetics
Cytogenetics is the study of chromosomes and chromosomal abnormalities. While cytogenetics has historically relied on microscopy to analyze chromosomes, new molecular technologies such as comparative genomic hybridization of arrays are now becoming widely used. Examples of chromosomal abnormalities include aneuploidy, chromosome rearrangement, and genomic deletion/duplication disorders.
Molecular genetics
Molecular genetics involves the discovery and laboratory testing of DNA mutations that underlie many single gene disorders. Examples of single gene disorders include achondroplasia, cystic fibrosis, Duchenne muscular dystrophy, hereditary breast cancer (BRCA1/2), Huntington's disease, Marfan syndrome, Noonan syndrome, and Rett syndrome. Molecular tests are also used in the diagnosis of syndromes involving epigenetic abnormalities, such as Angelman's syndrome, Beckwith-Wiedemann syndrome, Prader-willi syndrome, and uniparental discomfort.
Mitochondrial Genetics
Mitochondrial genetics involves the diagnosis and management of mitochondrial disorders, which have a molecular basis but often lead to biochemical abnormalities due to insufficient energy production.
There is some overlap between the medical genetic diagnostic laboratory and the molecular pathology.
Maps Medical genetics
Genetic Counseling
Genetic counseling is the process of providing information about genetic conditions, diagnostic tests, and risks to other family members, within the framework of nondirective counseling. Genetic counselors are non-physician members of the medical genetic team who specialize in family risk assessment and patient counseling about genetic disorders. The exact role of a genetic counselor varies depending on the disorder.
History
Although genetics had its roots back in the 19th century with the work of Bohemian monk Gregor Mendel and other pioneering scientists, human genetics emerged later. It began to develop, albeit slowly, during the first half of the 20th century. Mendelian (single-gen) inheritance is studied in a number of important disorders such as albinism, brachydactyly (short fingers and legs), and hemophilia. The mathematical approach is also designed and applied to human genetics. Population genetics have been created.
Medical genetics was a late developer, emerging largely after the close of World War II (1945) when the eugenics movement had fallen into a bad reputation. The Nazi abuse of eugenics sounded the death knell. Shaved from eugenics, a scientific approach can be used and applied to human and medical genetics. Medical genetics saw a rapid increase in the second half of the 20th century and continued into the 21st century.
Current practice
The clinical setting in which the patient is evaluated determines the scope of practice, diagnostics, and therapeutic interventions. For general discussion, typical meetings between patients and genetic practitioners may involve:
- Referral to an outpatient (pediatric, adult, or joint) genetics clinic or hospital consultation, most often for diagnostic evaluation.
- Special genetic clinics that focus on the management of innate metabolic error, skeletal dysplasia, or lysosomal storage disease.
- Referral for counseling at prenatal genetic clinics to discuss risks to pregnancy (elderly age, teratogen exposure, family history of genetic diseases), test results (abnormal maternal serum screen, abnormal ultrasound), and/or option for prenatal diagnosis amniocentesis or sampling of chorionic villi).
- A multidisciplinary specialist clinic that includes a clinical geneticist or genetic counselor (cancer genetics, cardiovascular genetics, craniofacial or cleft lip/palate, hearing loss clinic, muscular dystrophy/neurodegenerative disorder clinic).
Diagnostic evaluation
Each patient will undergo diagnostic evaluation tailored to their specific signs and symptoms. The geneticist will establish a differential diagnosis and recommend appropriate testing. These tests may evaluate for chromosomal disorders, innate metabolic errors, or single gene disorders.
Study of chromosomes
Chromosome studies are used in general genetic clinics to determine the cause of developmental delay/mental retardation, birth defects, dysmorphic features, and/or autism. Chromosome analysis is also performed in a prenatal setting to determine whether the fetus is affected by rearrangement of aneuploidy or other chromosomes. Finally, chromosomal abnormalities are often detected in cancer samples. A large number of different methods have been developed for chromosome analysis:
- Chromosome analysis using a karyotype involves a special stain that produces bright and dark bands, enabling the identification of each chromosome under a microscope.
- In situ fluorescence hybridization (FISH) involves labeling of fluorescent probes binding to specific DNA sequences, used to identify aneuploidy, genomic deletion or duplication, characterization of chromosomal translocation and determining the origin of ring chromosomes.
- Chromosome painting is a technique that uses a specific fluorescent probe for each chromosome to distinguish the labels of each chromosome. This technique is more commonly used in cancer cytogenetics, where complex chromosome rearrangements may occur.
- Comparative genomic hybridization array is a new molecular technique that involves the hybridization of individual DNA samples into glass slides or microarray chips containing molecular probes (ranging from large-artificial chromosomes ~ 200kb to small oligonucleotides) representing unique regions of the genome.. This method is very sensitive to detect genomic gain or loss across the genome but does not detect balanced translocation or distinguish the location of duplicated genetic material (eg, tandem duplication versus duplicate insertion).
Basic metabolic studies
Biochemical studies were performed to filter out the metabolite imbalance in body fluids, usually blood (plasma/serum) or urine, but also in cerebrospinal fluid (CSF). Special tests of enzyme function (either in leukocytes, skin fibroblasts, liver, or muscle) are also used in certain circumstances. In the US, newborn screens incorporate biochemical tests to screen for treatable conditions such as galactosemia and phenylketonuria (PKU). Patients presumed to have metabolic conditions may undergo the following tests:
- Quantitative amino acid analysis is usually performed using a ninhydrin reaction, followed by liquid chromatography to measure the amount of amino acid in the sample (either urine, plasma/serum, or CSF). Amino acid measurements in plasma or serum are used in the evaluation of metabolic disorders of amino acids such as urea cycle disorders, maple syrup urine, and PKU. Measurement of amino acids in urine can be useful in the diagnosis of cystinuria or renal Fanconi syndrome as seen in cystinosis.
- The analysis of urine organic acids can be done using quantitative or qualitative methods, but in both cases these tests are used to detect abnormal organic acid excretion. These compounds are usually produced during the body metabolism of amino acids and odd-chain fatty acids, but accumulate in patients with certain metabolic conditions.
- The combination profile of acylcarnitine detects compounds such as organic acids and fatty acids that are conjugated to carnitine. This test is used to detect disorders involving fatty acid metabolism, including MCAD.
- Pyruvate and lactate are byproducts of normal metabolism, especially during anaerobic metabolism. These compounds usually accumulate during exercise or ischemia, but also increase in patients with impaired pyruvate metabolism or mitochondrial disorders.
- Ammonia is the end product of amino acid metabolism and converted in the liver to urea through a series of enzymatic reactions called urea cycles. Elevated ammonia can be detected in patients with urea cycle disorders, as well as other conditions involving liver failure.
- The testing enzyme is performed for various metabolic disorders to confirm a suspected diagnosis based on screening tests.
Molecular studies
- DNA sequencing is used to directly analyze a series of DNA genomes from a particular gene. In general, only parts of the gene encode the expressed protein (exon) and a small number of untranslated regions and the analyzed introns. Therefore, although these tests are very specific and sensitive, they do not routinely identify all the mutations that can cause the disease.
- DNA methylation analysis is used to diagnose certain genetic disorders caused by impaired epigenetic mechanisms such as genomic inclusion and uniparental disomy.
- Southern blotting is the first basic technique for detection of DNA fragments separated by size through gel electrophoresis and detected using radiolabel probes. This test is routinely used to detect deletion or duplication in conditions such as Duchenne muscular dystrophy but is being replaced by comparative comparison comparative genomic comparison techniques. Southern blotting is still useful in the diagnosis of disorders caused by trinucleotide repeats.
- Short tandem repetition is a unique marker that can be used to define a haplotype and is used in identity testing for maternal cell contamination.
Treatment
Every cell of the body contains information of offspring (DNA) that is enclosed in a structure called a chromosome. Because genetic syndromes are usually the result of chromosomal or gene changes, no treatment is available today that can improve the genetic changes in every cell of the body. Therefore, there is currently no "cure" for genetic disorders. However, for many genetic syndromes there are treatments available to manage the symptoms. In some cases, especially congenital metabolic error, the disease mechanism is well understood and offers potential for food and medical management to prevent or reduce long-term complications. In other cases, infusion therapy is used to replace missing enzymes. Current research is actively looking to use gene therapy or other new drugs to treat certain genetic disorders.
Management of metabolic disorders
In general, metabolic disorders arise from deficiency of enzymes that interfere with normal metabolic pathways. For example, in the hypothetical example:
A --- & gt; B --- & gt; C --- & gt; D AAAA --- & gt; BBBBBB --- & gt; CCCCCCCCCC --- & gt; (nod)   X¡Â X Y Z Z Y (no Z)
The compound "A" is metabolized to "B" by the enzyme "X", the compound "B" is metabolized to "C" by the "Y" enzyme, and the compound "C" is metabolized to "D" by the enzyme "Z". If the "Z" enzyme is lost, the compound "D" will disappear, while the compounds "A", "B", and "C" will increase. The pathogenesis of this particular condition can occur due to the lack of "D" compounds, if very important for some cellular functions, or from toxicity due to excess "A", "B", and/or "C". Treatment of metabolic disorders can be achieved through dietary supplementation of the compound "D" and dietary restriction of compounds "A", "B", and/or "C" or by treatment with drugs that promote excess "A", "B" or "C ". Another approach to take is enzyme replacement therapy, in which a patient is given a missing enzyme infusion.
- Diet
Dietary restriction and supplementation are the main steps taken in some of the notable metabolic disorders, including galactosemia, phenylketonuria (PKU), maple syrup urine disease, organic acidurias and urea cycle disorders. Such tight diets can be difficult for patients and families to maintain, and require close consultation with nutritionists who have specific experience in metabolic disorders. The composition of the food will change depending on the calorie needs of the growing child and special attention is required during pregnancy if a woman is exposed to any of these disorders.
- Medication
Medical approaches include increased residual enzyme activity (in cases where enzymes are made but not functioning properly), inhibition of other enzymes in biochemical pathways to prevent the buildup of toxic compounds, or the transfer of toxic compounds into other forms that can be excreted. Examples include the use of high doses of pyridoxine (vitamin B6) in some patients with homocystinuria to increase the activity of residual cystathione synthase enzymes, biotin administration to restore the activity of some enzymes that are affected by biotinidase deficiency, treatment with NTBC in Tyrosinemia to inhibit succinylacetone production that causes liver toxicity, and the use of sodium benzoate to reduce the formation of ammonia in urea cycle disorders.
- Enzyme replacement therapy
Certain lysosomal storage diseases are treated with infusions of recombinant enzymes (produced in the laboratory), which can reduce the accumulation of compounds in various tissues. Examples include Gaucher's disease, Fabry's disease, Mucopolysaccharidoses and type II Glycogen storage diseases. Such treatment is limited by the ability of the enzyme to reach the affected area (blood brain barrier prevents enzymes reaching the brain, for example), and can sometimes be attributed to allergic reactions. The long-term clinical effectiveness of enzyme replacement therapy varies greatly among different disorders.
Another example
- angiotensin receptor blockers in Marfan syndrome & amp; Loeys-Dietz
- Bone marrow transplantation
- Gene therapy
Career path and training
There are various career paths in the field of medical genetics, and of course the training required for each field is very different. The information included in this section applies to typical trails in the United States and there may be differences in other countries. US practitioners in clinical subspecialty, counseling, or diagnostics generally obtain board certification through the American Board of Medical Genetics.
Genetic information provides a unique kind of knowledge about individuals and their families, essentially different from laboratory tests that usually provide a "snapshot" of an individual's health status. The unique status of genetic information and hereditary diseases has a number of consequences with respect to ethical, legal, and social issues.
On March 19, 2015, scientists urged worldwide ban on the use of clinical methods, especially the use of CRISPR and zinc fingers, to edit human genes in a heritable way. In April 2015 and April 2016, Chinese researchers reported basic research results for the editing of human embryonic DNA that could not live using CRISPR. In February 2016, British scientists were given permission by regulators to genetically modify human embryos using CRISPR and associated techniques on the condition that the embryo is destroyed within seven days. In June 2016 the Dutch government reportedly planned to follow it with a similar rule that would set a 14 day limit.
Society
A more empirical approach to human and medical genetics was formalized by the founding of the American Society of Human Genetics in 1948. The institute first began its annual meeting of that year (1948) and its international counterpart, the International Congress of Human Genetics, has met every 5 years since it was founded in 1956. The institute publishes the American Journal of Human Genetics on a monthly basis.
Medical genetics is now recognized as a distinct medical specialization in the US with its self-approved board (American Board of Medical Genetics) and the American College of Medical Genetics. Colleges hold annual scientific meetings, publish monthly journals, Genetics in Medicine , and publish term papers and clinical practice guides on topics relevant to human genetics.
Research
Various studies in medical genetics reflect the overall scope of this field, including basic research on genetic inheritance and human genome, mechanisms of genetic disorders and metabolism, translation research on new treatment modalities, and the impact of genetic testing.
Basic genetic research
The basic research geneticists typically conduct research at universities, biotechnology companies and research institutes.
Architecture allelic disease
Sometimes the relationship between the disease and the unusual variant of the gene is smoother. The genetic architecture of common diseases is an important factor in determining the extent to which patterns of genetic variation affect group differences in health outcomes. According to general diseases/common variants of the hypothesis, common variants present in the ancestral population before the spreading of modern humans from Africa play an important role in human disease. Genetic variations associated with Alzheimer's disease, deep vein thrombosis, Crohn's disease, and type 2 diabetes appear to follow this model. However, model generalities have not been established and, in some cases, are in doubt. Some diseases, such as many common cancers, do not appear to be well described by common ailments/general variant models.
Another possibility is that common illnesses arise partly through the action of a combination of variants that rarely occur individually. Most of the disease-related alleles found to date are rarely found, and rare variants are more likely than common variants to be distributed differently among groups distinguished by ancestors. However, groups may have differences, though perhaps overlapping, sets of rare variants, which will reduce the contrast between groups in the incidence of the disease.
The number of variants that contribute to the disease and the interactions among these variants may also affect the distribution of the disease among the groups. The difficulty that has been encountered in finding donor alleles for complex diseases and in replicating positive associations suggests that many complex diseases involve many variants rather than moderate allele numbers, and the effect of the given variant may depend on critical ways in the genetic and environmental background. If many alleles are required to increase susceptibility to an illness, it is likely that the combined allele required will be concentrated in a certain group purely by aberrations.
Population substructure in genetic research
One area where the population category can be an important consideration in genetic research is in controlling the mixing between population substructure, environmental exposure, and health outcomes. Associate studies can produce false results if cases and controls have different allele frequencies for genes unrelated to the disease being studied, although the magnitude of these problems in the study of genetic associations is debated. Various methods have been developed to detect and take into account population substructure, but this method can be difficult to apply in practice.
Population substructures can also be used to benefit in the study of genetic associations. For example, populations representing the latest mix of geographically separated groups of ancestors can show a long-distance imbalance between vulnerable alleles and genetic markers rather than cases for other populations. Genetic studies can use this mixed match fit to look for disease alleles with fewer markers than necessary. Associate studies can also draw on contrast experiences of racial or ethnic groups, including migrant groups, to look for interactions between specific alleles and environmental factors that might affect health.
See also
- Full genome sequencing
- Default metabolic error
- Predictive drugs
References
Further reading
- Peter Harper; Lois Reynolds; Tilli Tansey, eds. (2010), Clinical Genetics in the UK: Origin and development , Wellcome Witness Contemporary Medicine, History of Modern Biomedical Research Group, ISBN 978-0-85484-127-1 , Ã, Wikidata Q29581774
External links
- Genetic home reference
- The National Human Genome Research Institute becomes an information center
- The Phenomizer - A tool for clinical diagnosis in medical genetics. Phenomizer
Source of the article : Wikipedia
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