Medical genetics is the branch tics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of

genetic disorders A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics. In contrast, the study of typically non-medical

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

s 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 Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino. Varied use and interpretation of the term ...

). ''Genetic medicine'' is a newer term for medical genetics and incorporates areas such as

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...

personalized medicine Personalized medicine, also referred to as precision medicine, is a medical model that separates people into different groups—with medical decisions, practices, interventions and/or products being tailored to the individual patient based on the ...

, and the rapidly emerging new medical specialty, predictive medicine. Autosomal dominant and recessive

Scope

Medical genetics encompasses many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinical diagnostic laboratory activities, and research into the causes and inheritance of genetic disorders. Examples of conditions that fall within the scope of medical genetics include

birth defects A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

and

dysmorphology Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The relate ...

intellectual disabilities Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...

, autism, mitochondrial disorders,

skeletal dysplasia Osteochondrodysplasia is a general term for a disorder of the development (dysplasia) of bone ("osteo") and cartilage ("chondro"). Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia. Non ...

connective tissue disorder A connective tissue disease (collagenosis) is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds togeth ...

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

genetics, and

prenatal diagnosis Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of ...

. Medical genetics is increasingly becoming relevant to many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances in

genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...

are revealing etiologies for morphologic, endocrine,

cardiovascular The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

pulmonary The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of ...

, ophthalmologist,

renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

psychiatric Psychiatry is the medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psychiatry. Initial psy ...

, and dermatologic conditions. The medical genetics community is increasingly involved with individuals who have undertaken

elective genetic and genomic testing Elective may refer to: *Choice, the mental process of judging the merits of multiple options and selecting one of them *Elective course in education ** Elective (medical), a period of study forming part of a medical degree * In medical procedures, ...

Subspecialties

In some ways, many of the individual fields within medical genetics are hybrids between clinical care and research. This is due in part to recent advances in science and technology (for example, see the Human Genome Project) that have enabled an unprecedented understanding of

Clinical genetics

Clinical genetics a

medical specialty A medical specialty is a branch of medical practice that is focused on a defined group of patients, diseases, skills, or philosophy. Examples include those branches of medicine that deal exclusively with children (paediatrics), cancer (oncology), ...

with particular attention to

hereditary disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

s. Branches of clinical genetics include: :1. Prenatal genetics ::* Couples at risk of having a child with a genetic disorder preconception or while pregnant ::* High risk

prenatal screening Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health o ...

results ::* Abnormal fetal ultrasound :2. Pediatric genetics ::*

Birth defects A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

::*

Developmental disability Developmental disability is a diverse group of chronic conditions, comprising mental or physical impairments that arise before adulthood. Developmental disabilities cause individuals living with them many difficulties in certain areas of life, espe ...

, autism,

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

::*

short stature Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ' ...

and

:3. Adult genetics ::* cardiomyopathy and

cardiac dysrhythmias Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

::*inherited kidney disease ::*

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

and neurodegeneration ::*

connective tissue disease A connective tissue disease (collagenosis) is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds togeth ...

:4. Cancer genetics ::* breast/ovarian cancer ::*

bowel cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

::* endocrine tumors Examples of genetic syndromes that are commonly seen in the genetics clinic include chromosomal rearrangements (eg

Down syndrome Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...

, 22q11.2 deletion syndrome,

Turner syndrome Turner syndrome (TS), also known as 45,X, or 45,X0, is a genetic condition in which a female is partially or completely missing an X chromosome. Signs and symptoms vary among those affected. Often, a short and webbed neck, low-set ears, low hair ...

Williams syndrome Williams syndrome (WS) is a genetic disorder that affects many parts of the body. Facial features frequently include a broad forehead, underdeveloped chin, short nose, and full cheeks. Mild to moderate intellectual disability is observed in people ...

), Fragile X syndrome, Marfan syndrome,

neurofibromatosis Neurofibromatosis (NF) is a group of three conditions in which tumors grow in the nervous system. The three types are neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis. In NF1 symptoms include light brown sp ...

Huntington disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an unst ...

familial adenomatous polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition in which numerous adenomatous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon ...

, and many more.

Training and qualification

In the United States, doctors who practice clinical genetics are accredited by the American Board of Medical Genetics and Genomics (ABMGG). In order to become a board-certified practitioner of Clinical Genetics, a physician must complete a minimum of 24 months of training in a program accredited by the ABMGG. Individuals seeking acceptance into clinical genetics training programs must hold an M.D. or D.O. degree (or their equivalent) and have completed a minimum of 12 months of training in an

ACGME The Accreditation Council for Graduate Medical Education (ACGME) is the body responsible for accrediting all graduate medical training programs (i.e., internships, residencies, and fellowships, a.k.a. subspecialty programs) for physicians in the ...

-accredited

residency Residency may refer to: * Domicile (law), the act of establishing or maintaining a residence in a given place ** Permanent residency, indefinite residence within a country despite not having citizenship * Residency (medicine), a stage of postgra ...

program in internal medicine, pediatrics, obstetrics and gynecology, or other medical specialty. In Australia and New Zealand, clinical genetics is a three-year advanced training program for those who already have their primary medical qualification ( MBBS or MD) and have successfully completed basic training in either paediatric medicine or adult medicine. Training is overseen by the

Royal Australasian College of Physicians The Royal Australasian College of Physicians (RACP) is a not-for-profit professional organisation responsible for training and educating physicians and paediatricians across Australia and New Zealand. The RACP is responsible for training both ...

with the

Australasian Association of Clinical Geneticists The Australasian Association of Clinical Geneticists (AACG) is a professional membership organization for medical specialists who are qualified to work in the field of clinical genetics. The Association was founded in 1995. As of 2021, the organi ...

contributing to authorship of the curriculum via their parent organization, the Human Genetics Society of Australasia.

Metabolic/biochemical genetics

Metabolic (or biochemical) genetics involves the diagnosis and management of

inborn errors of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substra ...

in which patients have enzymatic deficiencies that perturb biochemical pathways involved in metabolism of carbohydrates, amino acids, and

lipids Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...

. Examples of metabolic disorders include

galactosemia Galactosemia (British galactosaemia, from Greek γαλακτόζη + αίμα, meaning galactose + blood, accumulation of galactose in blood) is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galacto ...

, glycogen storage disease,

lysosomal storage disorder Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys ...

peroxisomal disorders Peroxisomal disorders represent a class of medical conditions caused by defects in peroxisome functions. This may be due to defects in single enzymes important for peroxisome function or in peroxins, proteins encoded by ''PEX'' genes that are crit ...

phenylketonuria Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also re ...

, and

urea cycle disorder Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important r ...

Cytogenetics

Cytogenetics is the study of

chromosomes A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

and

chromosome abnormalities A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...

. While cytogenetics historically relied on microscopy to analyze chromosomes, new molecular technologies such as

array comparative genomic hybridization Comparative genomic hybridization (CGH) is a molecular cytogenetic method for analysing copy number variations (CNVs) relative to ploidy level in the DNA of a test sample compared to a reference sample, without the need for culturing cells. The a ...

are now becoming widely used. Examples of chromosome abnormalities include

aneuploidy Aneuploidy is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes. A cell with any ...

, chromosomal rearrangements, and genomic deletion/duplication disorders.

Molecular genetics

Molecular genetics involves the discovery of and laboratory testing for DNA mutations that underlie many single gene disorders. Examples of single gene disorders include

achondroplasia Achondroplasia is a genetic disorder with an autosomal dominant pattern of inheritance whose primary feature is dwarfism. In those with the condition, the arms and legs are short, while the torso is typically of normal length. Those affected ha ...

, cystic fibrosis,

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis follow ...

, hereditary

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

(BRCA1/2),

, Marfan syndrome,

Noonan syndrome Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. Facial features include widely spaced eyes, light-colored ...

, and

Rett syndrome Rett syndrome (RTT) is a genetic disorder that typically becomes apparent after 6–18 months of age and almost exclusively in females. Symptoms include impairments in language and coordination, and repetitive movements. Those affected often h ...

. Molecular tests are also used in the diagnosis of syndromes involving epigenetic abnormalities, such as Angelman syndrome, Beckwith-Wiedemann syndrome, Prader-willi syndrome, and

uniparental disomy Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or of part of a chromosome, from one parent and no copy from the other parent. UPD can be the result of heterodisomy, in which a pair of non-identical chromosomes ar ...

Mitochondrial genetics

Mitochondrial genetics concerns the diagnosis and management of mitochondrial disorders, which have a molecular basis but often result in biochemical abnormalities due to deficient energy production. 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.

Genetic counselor Genetic counseling is the process of investigating individuals and families affected by or at risk of genetic disorders to help them understand and adapt to the medical, psychological and familial implications of genetic contributions to disease; t ...

s are non-physician members of the medical genetics team who specialize in family risk assessment and counseling of patients regarding genetic disorders. The precise role of the genetic counselor varies somewhat depending on the disorder. When working alongside geneticists, genetic counselors normally specialize in pediatric genetics which focuses on developmental abnormalities present in newborns, infants or children. The major goal of pediatric counseling is attempting to explain the genetic basis behind the child's developmental concerns in a compassionate and articulated manner that allows the potentially distressed or frustrated parents to easily understand the information. As well, genetic counselors normally take a family pedigree, which summarizes the medical history of the patient's family. This then aids the clinical geneticist in the differential diagnosis process and help determine which further steps should be taken to help the patient.

History

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

Gregor Mendel Gregor Johann Mendel, OSA (; cs, Řehoř Jan Mendel; 20 July 1822 – 6 January 1884) was a biologist, meteorologist, mathematician, Augustinian friar and abbot of St. Thomas' Abbey in Brünn (''Brno''), Margraviate of Moravia. Mendel was ...

and other pioneering scientists, human genetics emerged later. It started to develop, albeit slowly, during the first half of the 20th century. Mendelian (single-gene) inheritance was studied in a number of important disorders such as albinism,

brachydactyly Brachydactyly (Greek βραχύς = "short" plus δάκτυλος = "finger"), is a medical term which literally means "short finger". The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an in ...

(short fingers and toes), and hemophilia. Mathematical approaches were also devised and applied to human genetics.

Population genetics Population genetics is a subfield of genetics that deals with genetic differences within and between populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as Adaptation (biology), adaptation, ...

was created. Medical genetics was a late developer, emerging largely after the close of

World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposing ...

(1945) when the

eugenics Eugenics ( ; ) is a fringe set of beliefs and practices that aim to improve the genetic quality of a human population. Historically, eugenicists have attempted to alter human gene pools by excluding people and groups judged to be inferior o ...

movement had fallen into disrepute. The Nazi misuse of eugenics sounded its death knell. 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

, or

lysosomal storage diseases Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest large molecules and pass the fragments on to other ...

. * Referral for counseling in a prenatal genetics clinic to discuss risks to the pregnancy (

advanced maternal age Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.differential diagnosis and recommend appropriate testing. These tests might evaluate for

chromosomal A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

disorders,

, or single gene disorders.

Chromosome studies

Human karyotype with bands and sub-bands

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. 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 Fluorescence ''in situ'' hybridization (FISH) is a molecular cytogenetic technique that uses fluorescent probes that bind to only particular parts of a nucleic acid sequence with a high degree of sequence complementarity. It was developed by ...

(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 chromosome A ring chromosome is an aberrant chromosome whose ends have fused together to form a ring. Ring chromosomes were first discovered by Lilian Vaughan Morgan in 1926. A ring chromosome is denoted by the symbol ''r'' in human genetics and ''R'' in '' ...

s. * 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 Comparative genomic hybridization (CGH) is a molecular cytogenetic method for analysing copy number variations (CNVs) relative to ploidy level in the DNA of a test sample compared to a reference sample, without the need for culturing cells. The a ...

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 chromosome A bacterial artificial chromosome (BAC) is a DNA construct, based on a functional fertility plasmid (or F-plasmid), used for transforming and cloning in bacteria, usually '' E. coli''. F-plasmids play a crucial role because they contain partiti ...

s 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).

Basic metabolic studies

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

and

(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

liquid chromatography In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...

to measure the amount of amino acid in the sample (either urine, plasma/serum, or CSF). Measurement of amino acids in plasma or serum is used in the evaluation of disorders of amino acid metabolism such as urea cycle disorders,

maple syrup urine disease Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine and ear ...

, and

PKU Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also resu ...

. Measurement of amino acids in urine can be useful in the diagnosis of

cystinuria Cystinuria is an inherited autosomal recessive disease characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureters, and bladder. It is a type of aminoaciduri ...

or renal

Fanconi syndrome Fanconi syndrome or Fanconi's syndrome (, ) is a syndrome of inadequate reabsorption in the proximal renal tubules of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity (for example, from tox ...

as can be seen in

cystinosis Cystinosis is a lysosomal storage disease characterized by the abnormal accumulation of cystine, the oxidized dimer of the amino acid cysteine. It is a genetic disorder that follows an autosomal recessive inheritance pattern. It is a rare autosom ...

. * 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

organic acids An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids, whose acidity is associated with their carboxyl group –COOH. Sulfonic acids, containing the group –SO2OH, are r ...

. These compounds are normally produced during bodily metabolism of amino acids and odd-chain fatty acids, but accumulate in patients with certain 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 Anaerobic respiration is respiration using electron acceptors other than molecular oxygen (O2). Although oxygen is not the final electron acceptor, the process still uses a respiratory electron transport chain. In aerobic organisms undergoing r ...

. These compounds normally accumulate during exercise or ischemia, but are also elevated in patients with disorders of pyruvate metabolism or mitochondrial disorders. *

Ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...

is an end product of amino acid metabolism and is converted in the liver to

urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...

through a series of enzymatic reactions termed the

urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of Biochemistry, biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle ...

. Elevated ammonia can therefore be detected in patients with 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.

Molecular studies

* DNA sequencing is used to directly analyze the genomic DNA sequence of a particular gene. In general, only the parts of the gene that code for the expressed protein ( exons) and small amounts of the flanking untranslated regions and

introns An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene ...

are analyzed. Therefore, although these tests are highly specific and sensitive, they do not routinely identify all of the mutations that could cause disease. * DNA methylation analysis is used to diagnose certain genetic disorders that are caused by disruptions of epigenetic mechanisms such as genomic imprinting and

. *

Southern blotting A Southern blot is a method used in molecular biology for detection of a specific DNA sequence in DNA samples. Southern blotting combines transfer of electrophoresis-separated DNA fragments to a filter membrane and subsequent fragment detecti ...

is an early technique basic on detection of fragments of DNA separated by size through gel electrophoresis and detected using radiolabeled probes. This test was routinely used to detect deletions or duplications in conditions such as

but is being replaced by high-resolution

techniques. Southern blotting is still useful in the diagnosis of disorders caused by trinucleotide repeats.

Treatments

Each cell of the body contains the hereditary information ( DNA) wrapped up in structures called

. Since genetic syndromes are typically the result of alterations of the chromosomes or genes, there is no treatment currently available that can correct the genetic alterations in every cell of the body. Therefore, there is currently no "cure" for genetic disorders. However, for many genetic syndromes there is treatment available to manage the symptoms. In some cases, particularly

, the mechanism of disease is well understood and offers the potential for dietary and medical management to prevent or reduce the long-term complications. In other cases,

infusion therapy In medicine, infusion therapy deals with all aspects of fluid and medication infusion, via intravenous or subcutaneous application. A special infusion pump can be used for this purpose. A fenestrated catheter is most frequently inserted into the lo ...

is used to replace the missing enzyme. Current research is actively seeking to use

or other new medications to treat specific genetic disorders.

Management of metabolic disorders

In general, metabolic disorders arise from enzyme deficiencies that disrupt normal metabolic pathways. For instance, in the hypothetical example: A ---> B ---> C ---> D AAAA ---> BBBBBB ---> CCCCCCCCCC ---> (no D) X Y Z X Y , (no or insufficient Z) EEEEE Compound "A" is metabolized to "B" by enzyme "X", compound "B" is metabolized to "C" by enzyme "Y", and compound "C" is metabolized to "D" by enzyme "Z". If enzyme "Z" is missing, compound "D" will be missing, while compounds "A", "B", and "C" will build up. The pathogenesis of this particular condition could result from lack of compound "D", if it is critical for some cellular function, or from toxicity due to excess "A", "B", and/or "C", or from toxicity due to the excess of "E" which is normally only present in small amounts and only accumulates when "C" is in excess. Treatment of the metabolic disorder could be achieved through dietary supplementation of compound "D" and dietary restriction of compounds "A", "B", and/or "C" or by treatment with a medication that promoted disposal of excess "A", "B", "C" or "E". Another approach that can be taken is enzyme replacement therapy, in which a patient is given an infusion of the missing enzyme "Z" or cofactor therapy to increase the efficacy of any residual "Z" activity. * Diet Dietary restriction and supplementation are key measures taken in several well-known metabolic disorders, including

(PKU),

, organic acidurias and urea cycle disorders. Such restrictive diets can be difficult for the patient and family to maintain, and require close consultation with a nutritionist who has special experience in metabolic disorders. The composition of the diet will change depending on the caloric needs of the growing child and special attention is needed during a pregnancy if a woman is affected with one of these disorders. * Medication Medical approaches include enhancement of residual enzyme activity (in cases where the enzyme is made but is not functioning properly), inhibition of other enzymes in the biochemical pathway to prevent buildup of a toxic compound, or diversion of a toxic compound to another form that can be excreted. Examples include the use of high doses of pyridoxine (vitamin B6) in some patients with

homocystinuria Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to i ...

to boost the activity of the residual cystathione synthase enzyme, administration of biotin to restore activity of several enzymes affected by deficiency of

biotinidase Biotinidase (, ''amidohydrolase biotinidase'', ''BTD''), also known as biotinase, is an enzyme that in humans is encoded by the ''BTD'' gene. The enzyme breaks down biotin amides, releasing free biotin and the amine. The main substrate is bioc ...

, treatment with NTBC in

Tyrosinemia Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms of untreated tyrosinemia include liver and kidney disturbances. Without treatment, tyrosinemi ...

to inhibit the production of succinylacetone which causes liver toxicity, and the use of

sodium benzoate Sodium benzoate is the sodium salt of benzoic acid, widely used as a food preservative (with an E number of E211) and a pickling agent. It appears as a white crystalline chemical with the formula C6H5COONa. Production Sodium benzoate is commo ...

to decrease

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous wa ...

build-up in urea cycle disorders. *

Enzyme replacement therapy Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme. ERT is availa ...

Certain

are treated with infusions of a recombinant enzyme (produced in a laboratory), which can reduce the accumulation of the compounds in various tissues. Examples include

Gaucher disease Gaucher's disease or Gaucher disease () (GD) is a genetic disorder in which glucocerebroside (a sphingolipid, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low ...

Fabry disease Fabry disease, also known as Anderson–Fabry disease, is a rare genetic disease that can affect many parts of the body, including the kidneys, heart, and skin. Fabry disease is one of a group of conditions known as lysosomal storage diseases. T ...

, Mucopolysaccharidoses and

Glycogen storage disease type II Glycogen storage disease type II, also called Pompe disease, is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of ...

. Such treatments are limited by the ability of the enzyme to reach the affected areas (the

blood brain barrier Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...

prevents enzyme from reaching the brain, for example), and can sometimes be associated with allergic reactions. The long-term clinical effectiveness of enzyme replacement therapies vary widely among different disorders.

Other examples

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

Career paths and training

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 CRISPR and

zinc finger A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...

, to edit the

human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the ...

in a way that can be inherited. In April 2015 and April 2016, Chinese researchers reported results of

basic research Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied rese ...

to edit the DNA of non-viable human embryos using CRISPR. In February 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR and related techniques on condition that the embryos were destroyed within seven days. In June 2016 the Dutch government was reported to be planning to follow suit with similar regulations which would specify a 14-day limit.

Societies

The more empirical approach to human and medical genetics was formalized by the founding in 1948 of the

American Society of Human Genetics The American Society of Human Genetics (ASHG), founded in 1948, is a professional membership organization for specialists in human genetics. As of 2009, the organization had approximately 8,000 members. The Society's members include researchers, a ...

. 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 The ''American Journal of Human Genetics'' is a monthly peer-reviewed scientific journal in the field of human genetics. It was established in 1948 by the American Society of Human Genetics and covers all aspects of heredity in humans, includin ...

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

American College of Medical Genetics The American College of Medical Genetics and Genomics (ACMG) is an organization composed of biochemical, clinical, cytogenetic, medical and molecular geneticists, genetic counselors and other health care professionals committed to the practice of ...

). The college holds an annual scientific meeting, publishes a monthly journal, ''

Genetics in Medicine ''Genetics in Medicine'' is a monthly peer-reviewed medical journal covering medical genetics. It is the official journal of the American College of Medical Genetics and Genomics (ACMG). It was established in 1998 and has been published jointly ...

'', and issues position papers and clinical practice guidelines on a variety of topics relevant to human genetics. In Australia and

New Zealand New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 smaller islands. It is the sixth-largest island count ...

, medical geneticists are trained and certified under the auspices of the

, but professionally belong to the Human Genetics Society of Australasia and its special interest group, the

, for ongoing education, networking and advocacy.

Research

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. 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. Genetic variants associated with Alzheimer disease, deep venous thrombosis, Crohn disease, and type 2 diabetes appear to adhere to this model. However, the generality of the model has not yet been established and, in some cases, is in doubt. Some diseases, such as many common cancers, appear not to be well described by the common disease/common variant model. Another possibility is that common diseases arise in part through the action of combinations of variants that are individually rare. 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. 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. 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.

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, environmental exposures, and health outcomes. Association studies can produce spurious results if cases and controls have differing allele frequencies for genes that are not related to the disease being studied, although the magnitude of this problem in genetic association studies is subject to debate. Various methods have been developed to detect and account for population substructure, but these methods can be difficult to apply in practice. Population substructure also can be used to advantage in genetic association studies. 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. 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.

References

External links

Genetics home reference
* The National Human Genome Research Institute hosts a
information center
* The Phenomizer – A tool for clinical diagnostics in medical genetics
Phenomizer
{{Genetics-footer Cancer research

Scope

Subspecialties

Clinical genetics

Training and qualification

Metabolic/biochemical genetics

Cytogenetics

Molecular genetics

Mitochondrial genetics

Genetic counseling

History

Current practice

Chromosome studies

Basic metabolic studies

Molecular studies

Treatments

Management of metabolic disorders

Other examples

Career paths and training

Ethical, legal and social implications

Societies

Research

Basic genetics research

Allelic architecture of disease

Population substructure in genetics research

See also

References

Further reading

External links