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 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 uniparental disomy. southern blotting 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 duchenne muscular dystrophy but is being replaced by high-resolution array comparative genomic hybridization 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 chromosomes. 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 inborn errors of metabolism, 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 is used to replace the missing enzyme. current research is actively seeking to use gene therapy 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 galactosemia, phenylketonuria (pku), maple syrup urine disease, 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 to boost the activity of the residual cystathione synthase enzyme, administration of biotin to restore activity of several enzymes affected by deficiency of biotinidase, treatment with ntbc in tyrosinemia to inhibit the production of succinylacetone which causes liver toxicity, and the use of sodium benzoate to decrease ammonia build-up in urea cycle disorders. enzyme replacement therapy certain lysosomal storage diseases 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, fabry disease, mucopolysaccharidoses and glycogen storage disease type ii. such treatments are limited by the ability of the enzyme to reach the affected areas (the blood brain barrier 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 geneticist working with a pedigreethere 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. careerdegreedescriptiontraining clinical geneticistmd, do, md-phd or mbbsa clinical geneticist is typically a physician who evaluates patients in the office or as a hospital consultation. this process includes a medical history, family history (pedigree), a detailed physical examination, reviewing objective data such as imaging and test results, establishing a differential diagnosis, and recommending appropriate diagnostic tests.college (4 yrs) → medical school (4 yrs) → primary residency (1 yr) → residency in clinical genetics (2 yrs). some clinical geneticists also obtain a phd degree (4-7 yrs). a new residency track offers a 4 yr primary residency in clinical genetics immediately after finishing medical school. genetic counselormsa genetic counselor specializes in communication of genetic information to patients and families. genetic counselors often work closely with clinical geneticists or other physicians (such as obstetricians or oncologists) and often convey the results of the recommended tests.college (4 yrs) → graduate program in genetic counseling (2 yrs). metabolic nurse and/or nutritionistba/bs, ms, rnone of the critical aspects of the management of patients with metabolic disorders is the appropriate nutritional intervention (either restricting the compound that cannot be metabolized, or supplementing compounds that are deficient as the result of an enzyme deficiency). the metabolic nurse and nutritionist play important roles in coordinating the dietary management.college (4 yrs) → nursing school or graduate training in nutrition. biochemical diagnosticsbs, ms, ph.d., md, do, md-phdindividuals who specialize in biochemical genetics typically work in the diagnostic laboratory, analyzing and interpreting specialized biochemical tests that measure amino acids, organic acids, and enzyme activity. some clinical geneticists are also board certified in biochemical genetics.college (4 yrs) → graduate school (phd, usually 4–7 years) and/or medical school (4 years) cytogenetic diagnosticsbs, ms, phd, md, do, md-phdindividuals who specialize in cytogenetics typically work in the diagnostic laboratory, analyzing and interpreting karyotypes, fish, and comparative genomic hybridization tests. some clinical geneticists are also board certified in cytogenetics.college (4 yrs) → graduate school (phd, usually 4–7 years) and/or medical school (4 years) molecular geneticsbs, ms, phd, md, do, md-phdindividuals who specialize in molecular genetics typically work in the diagnostic laboratory, analyzing and interpreting specialized genetic tests that look for disease-causing changes (mutations) in the dna. some examples of molecular diagnostic tests include dna sequencing and southern blotting.college (4 yrs) → graduate school (phd, usually 4–7 years) and/or medical school (4 years) research geneticistbs, ms, phd, md, do, md-phdany researcher who studies the genetic basis of human disease or uses model organisms to study disease mechanisms could be considered a research geneticist. many of the clinical career paths also include basic or translational research, and thus individuals in the field of medical genetics often participate in some form of research.college (4 yrs) → graduate school (phd, usually 4–7 years) and/or medical school (4 years) → post-doctoral research training (usually 3+ years) laboratory technicianas, bs, mstechnicians in the diagnostic or research labs handle samples and run the assays at the bench.college (4 yrs), may have higher degree (ms, 2+ years) 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, to edit the human genome in a way that can be inherited. in april 2015 and april 2016, chinese researchers reported results of basic research 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 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 american college of medical genetics). the college holds an annual scientific meeting, publishes a monthly journal, genetics in medicine, and issues position papers and clinical practice guidelines on a variety of topics relevant to human genetics. 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. 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 main article: population groups in biomedicine 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