Medical genetics

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Medical genetics is the branch of

In contrast, the study of typically non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism). Genetic medicine is a newer term for medical genetics and incorporates areas such as gene therapy, personalized medicine, and the rapidly emerging new medical specialty, predictive medicine.

Scope

Medical genetics encompasses many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinical

1.

Prenatal genetics

• Couples at risk of having a child with a genetic disorder preconception or while pregnant
• High risk
  prenatal screening
  results
• Abnormal fetal ultrasound

2. Pediatric genetics

• Birth defects
• autism, epilepsy
• skeletal dysplasia

3. Adult genetics

• cardiac dysrhythmias
• inherited kidney disease
• neurodegeneration
• connective tissue disease

4. Cancer genetics

• breast/ovarian cancer
• bowel cancer
• endocrine tumors

Examples of genetic syndromes that are commonly seen in the genetics clinic include

There exists some overlap between medical genetic diagnostic laboratories and molecular pathology.

Genetic counseling

Genetic counseling is the process of providing information about genetic conditions, diagnostic testing, and risks in other family members, within the framework of nondirective counseling.

History

Although genetics has its roots back in the 19th century with the work of the Bohemian monk

Medical genetics was a late developer, emerging largely after the close of World War II (1945) when the eugenics movement had fallen into disrepute.^[5] The Nazi misuse of eugenics sounded its death knell.^[6] Shorn of eugenics, a scientific approach could be used and was applied to human and medical genetics. Medical genetics saw an increasingly rapid rise in the second half of the 20th century and continues in the 21st century.

Current practice

The clinical setting in which patients are evaluated determines the scope of practice, diagnostic, and therapeutic interventions. For the purposes of general discussion, the typical encounters between patients and genetic practitioners may involve:

• Referral to an out-patient genetics clinic (pediatric, adult, or combined) or an in-hospital consultation, most often for diagnostic evaluation.
• Specialty genetics clinics focusing on management of
  lysosomal storage diseases
  .
• Referral for counseling in a prenatal genetics clinic to discuss risks to the pregnancy (advanced maternal age, teratogen exposure, family history of a genetic disease), test results (abnormal maternal serum screen, abnormal ultrasound), and/or options for prenatal diagnosis (typically non-invasive prenatal screening, diagnostic amniocentesis or chorionic villus sampling).
• Multidisciplinary specialty clinics that include a clinical geneticist or genetic counselor (cancer genetics, cardiovascular genetics, craniofacial or cleft lip/palate, hearing loss clinics, muscular dystrophy/neurodegenerative disorder clinics).

Diagnostic evaluation

Each patient will undergo a diagnostic evaluation tailored to their own particular presenting signs and symptoms. The geneticist will establish a

Chromosome studies are used in the general genetics clinic to determine a cause for developmental delay or intellectual disability, birth defects, dysmorphic features, or autism.^[citation needed] Chromosome analysis is also performed in the prenatal setting to determine whether a fetus is affected with aneuploidy or other chromosome rearrangements. Finally, chromosome 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 special stains that generate light and dark bands, allowing identification of each chromosome under a microscope.
• Fluorescence in situ hybridization (FISH) involves fluorescent labeling of probes that bind to specific DNA sequences, used for identifying aneuploidy, genomic deletions or duplications, characterizing chromosomal translocations and determining the origin of ring chromosomes.
• Chromosome painting is a technique that uses fluorescent probes specific for each chromosome to differentially label each chromosome. This technique is more often used in cancer cytogenetics, where complex chromosome rearrangements can occur.
• Array comparative genomic hybridization is a newer molecular technique that involves hybridization of an individual DNA sample to a glass slide or microarray chip containing molecular probes (ranging from large ~200kb bacterial artificial chromosomes
  to small oligonucleotides) that represent unique regions of the genome. This method is particularly sensitive for detection of genomic gains or losses across the genome but does not detect balanced translocations or distinguish the location of duplicated genetic material (for example, a tandem duplication versus an insertional duplication).

Biochemical studies are performed to screen for imbalances of metabolites in the bodily fluid, usually the blood (plasma/serum) or urine, but also in cerebrospinal fluid (CSF). Specific tests of enzyme function (either in leukocytes, skin fibroblasts, liver, or muscle) are also employed under certain circumstances. In the US, the newborn screen incorporates biochemical tests to screen for treatable conditions such as galactosemia and phenylketonuria (PKU). Patients suspected to have a metabolic condition might undergo the following tests:

• Quantitative amino acid analysis is typically performed using the ninhydrin reaction, followed by
  urea cycle disorders, maple syrup urine disease, and PKU. Measurement of amino acids in urine can be useful in the diagnosis of cystinuria or renal Fanconi syndrome as can be seen in cystinosis
  .
• Urine organic acid analysis can be either performed using quantitative or qualitative methods, but in either case the test is used to detect the excretion of abnormal
  metabolic conditions
  .
• The acylcarnitine combination profile detects compounds such as organic acids and fatty acids conjugated to carnitine. The test is used for detection of disorders involving fatty acid metabolism, including
  MCAD
  .
• Pyruvate and lactate are byproducts of normal metabolism, particularly during anaerobic metabolism. These compounds normally accumulate during exercise or ischemia, but are also elevated in patients with disorders of pyruvate metabolism or mitochondrial disorders.
• urea cycle disorders, as well as other conditions involving liver failure
  .
• Enzyme testing is performed for a wide range of metabolic disorders to confirm a diagnosis suspected based on screening tests.

• introns
  are analyzed. Therefore, although these tests are highly specific and sensitive, they do not routinely identify all of the mutations that could cause disease.
• epigenetic mechanisms such as genomic imprinting and uniparental disomy
  .
• trinucleotide repeats
  .

A ---> B ---> C ---> D AAAA ---> BBBBBB ---> CCCCCCCCCC ---> (no D)
X Y Z X Y | (no or insufficient Z)
EEEEE

• Enzyme replacement therapy

Certain

Other examples

• Angiotensin receptor blockers in Marfan syndrome & Loeys-Dietz
• Bone marrow transplantation
• Gene therapy

Career paths and training

The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. You may improve this article, discuss the issue on the talk page, or create a new article, as appropriate. (August 2015) (Learn how and when to remove this template message)

There are a variety of career paths within the field of medical genetics, and naturally the training required for each area differs considerably. The information included in this section applies to the typical pathways in the United States and there may be differences in other countries. US practitioners in clinical, counseling, or diagnostic subspecialties generally obtain board certification through the American Board of Medical Genetics.

Ethical, legal and social implications

Genetic information provides a unique type of knowledge about an individual and his/her family, fundamentally different from a typically laboratory test that provides a "snapshot" of an individual's health status. The unique status of genetic information and inherited disease has a number of ramifications with regard to ethical, legal, and societal concerns.

On 19 March 2015, scientists urged a worldwide ban on clinical use of methods, particularly the use of

The more empirical approach to human and medical genetics was formalized by the founding in 1948 of the American Society of Human Genetics. The Society first began annual meetings that year (1948) and its international counterpart, the International Congress of Human Genetics, has met every 5 years since its inception in 1956. The Society publishes the American Journal of Human Genetics on a monthly basis.

Medical genetics is recognized as a distinct medical specialty. In the U.S., medical genetics has its own approved board (the American Board of Medical Genetics) and clinical specialty college (the

In Australia and New Zealand, medical geneticists are trained and certified under the auspices of the Royal Australasian College of Physicians, but professionally belong to the Human Genetics Society of Australasia and its special interest group, the Australasian Association of Clinical Geneticists, for ongoing education, networking and advocacy.

bioethics

^[16]

Research

This section needs expansion with: more details and additional citations. You can help by adding to it. (August 2008)

The broad range of research in medical genetics reflects the overall scope of this field, including basic research on genetic inheritance and the human genome, mechanisms of genetic and metabolic disorders, translational research on new treatment modalities, and the impact of genetic testing

Basic genetics research

Basic research geneticists usually undertake research in universities, biotechnology firms and research institutes.

Allelic architecture of disease

Sometimes the link between a disease and an unusual gene variant is more subtle. The genetic architecture of common diseases is an important factor in determining the extent to which patterns of genetic variation influence group differences in health outcomes.^[17][18][19] According to the common disease/common variant hypothesis, common variants present in the ancestral population before the dispersal of modern humans from Africa play an important role in human diseases.^[20] Genetic variants associated with Alzheimer disease, deep venous thrombosis, Crohn disease, and type 2 diabetes appear to adhere to this model.^[21] However, the generality of the model has not yet been established and, in some cases, is in doubt.^[18][22][23] Some diseases, such as many common cancers, appear not to be well described by the common disease/common variant model.^[24]

Another possibility is that common diseases arise in part through the action of combinations of variants that are individually rare.^[25][26] Most of the disease-associated alleles discovered to date have been rare, and rare variants are more likely than common variants to be differentially distributed among groups distinguished by ancestry.^[24][27] However, groups could harbor different, though perhaps overlapping, sets of rare variants, which would reduce contrasts between groups in the incidence of the disease.

The number of variants contributing to a disease and the interactions among those variants also could influence the distribution of diseases among groups. The difficulty that has been encountered in finding contributory alleles for complex diseases and in replicating positive associations suggests that many complex diseases involve numerous variants rather than a moderate number of alleles, and the influence of any given variant may depend in critical ways on the genetic and environmental background.^{[22][28][29][30]} If many alleles are required to increase susceptibility to a disease, the odds are low that the necessary combination of alleles would become concentrated in a particular group purely through drift.^[31]

Population substructure in genetics research

One area in which population categories can be important considerations in genetics research is in controlling for confounding between

Population substructure also can be used to advantage in genetic association studies.[38] For example, populations that represent recent mixtures of geographically separated ancestral groups can exhibit longer-range linkage disequilibrium between susceptibility alleles and genetic markers than is the case for other populations.^{[39][40][41][42]} Genetic studies can use this admixture linkage disequilibrium to search for disease alleles with fewer markers than would be needed otherwise. Association studies also can take advantage of the contrasting experiences of racial or ethnic groups, including migrant groups, to search for interactions between particular alleles and environmental factors that might influence health.^[43][44]

See also

• Full genome sequencing
• Inborn error of metabolism
• Predictive medicine
• DNA Valley

References