Jump to content

Medical genetics

From Wikipedia, the free encyclopedia
"Clinical genetics" redirects here. For the journal, seeClinical Genetics (journal).
For a non-technical introduction to the topic, seeIntroduction to genetics.
Part of a series on
Genetics
Key components
History and topics
Research
Fields
Personalized medicine

Medical geneticsis the branch ofmedicinethat involves the diagnosis and management ofhereditary disorders.Medical genetics differs fromhuman geneticsin thathumangenetics 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 ofgenetic disorderswould 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-medicalphenotypessuch as thegeneticsof eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such asalbinism).Genetic medicineis a newer term for medical genetics and incorporates areas such asgene therapy,personalized medicine,and the rapidly emerging new medical specialty,predictive medicine.

Autosomal dominant and autosomal recessive inheritance, the two most commonMendelian inheritancepatterns. Anautosomeis any chromosome other than asex chromosome.

Scope[edit]

Medical geneticsencompasses many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinicaldiagnosticlaboratory activities, and research into the causes and inheritance of genetic disorders. Examples of conditions that fall within the scope of medical genetics includebirth defectsanddysmorphology,intellectual disabilities,autism,mitochondrialdisorders,skeletal dysplasia,connective tissue disorders,cancergenetics, andprenatal diagnosis.Medical genetics is increasingly becoming relevant to many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances ingeneticsare revealing etiologies formorphologic,endocrine,cardiovascular,pulmonary,ophthalmologist,renal,psychiatric,anddermatologicconditions. The medical genetics community is increasingly involved with individuals who have undertakenelective genetic and genomic testing.

Subspecialties[edit]

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 theHuman Genome Project) that have enabled an unprecedented understanding ofgenetic disorders.

Clinical genetics[edit]

Clinical genetics amedical specialtywith particular attention tohereditary disorders.Branches of clinical genetics include:

1.Prenatal genetics
  • Couples at risk of having a child with a genetic disorder preconception or while pregnant
  • High riskprenatal screeningresults
  • Abnormal fetal ultrasound
2. Pediatric genetics
3. Adult genetics
4. Cancer genetics

Examples of genetic syndromes that are commonly seen in the genetics clinic includechromosomal rearrangements(e.g.Down syndrome,22q11.2 deletion syndrome,Turner syndrome,Williams syndrome),Fragile X syndrome,Marfan syndrome,neurofibromatosis,Huntington disease,familial adenomatous polyposis,and many more.

Training and qualification[edit]

In theUnited States,physicians who practice clinical genetics are accredited by the American Board of Medical Genetics and Genomics (ABMGG).[1]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 anACGME-accreditedresidencyprogram ininternal medicine,pediatrics,obstetrics and gynecology,or other medical specialty.[2]

InAustralia and New Zealand,clinical genetics is a three-year advanced training program for those who already have their primary medical qualification (MBBSorMD) and have successfully completed basic training in eitherpaediatric medicineoradult medicine.Training is overseen by theRoyal Australasian College of Physicianswith theAustralasian Association of Clinical Geneticistscontributing to authorship of the curriculum via their parent organization, theHuman Genetics Society of Australasia.[3]

Metabolic/biochemical genetics[edit]

Metabolic(or biochemical) genetics involves the diagnosis and management ofinborn errors of metabolismin which patients have enzymatic deficiencies that perturbbiochemicalpathways involved in metabolism ofcarbohydrates,amino acids,andlipids.Examples of metabolic disorders includegalactosemia,glycogen storage disease,lysosomal storage disorders,metabolic acidosis,peroxisomal disorders,phenylketonuria,andurea cycle disorders.

Cytogenetics[edit]

Cytogenetics is the study ofchromosomesandchromosome abnormalities.While cytogenetics historically relied onmicroscopyto analyze chromosomes, new molecular technologies such asarray comparative genomic hybridizationare now becoming widely used. Examples of chromosome abnormalities includeaneuploidy,chromosomal rearrangements,and genomic deletion/duplication disorders.

Molecular genetics[edit]

Molecular genetics involves the discovery of and laboratory testing forDNAmutations that underlie manysingle gene disorders.Examples of single gene disorders includeachondroplasia,cystic fibrosis,Duchenne muscular dystrophy,hereditarybreast cancer(BRCA1/2),Huntington disease,Marfan syndrome,Noonan syndrome,andRett syndrome.Molecular tests are also used in the diagnosis of syndromes involvingepigeneticabnormalities, such asAngelman syndrome,Beckwith-Wiedemann syndrome,Prader-willi syndrome,anduniparental disomy.

Mitochondrial genetics[edit]

Mitochondrialgenetics concerns the diagnosis and management ofmitochondrialdisorders, 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 andmolecular pathology.

Genetic counseling[edit]

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 counselorsare 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.[4]

History[edit]

Although genetics has its roots back in the 19th century with the work of the Bohemian monkGregor Mendeland 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(short fingers and toes), andhemophilia.Mathematical approaches were also devised and applied to human genetics.Population geneticswas created.

Medical genetics was a late developer, emerging largely after the close ofWorld War II(1945) when theeugenicsmovement 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[edit]

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 ofinborn errors of metabolism,skeletal dysplasia,orlysosomal 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[edit]

Each patient will undergo a diagnostic evaluation tailored to their own particular presenting signs and symptoms. The geneticist will establish adifferential diagnosisand recommend appropriate testing. These tests might evaluate forchromosomaldisorders,inborn errors of metabolism,or single gene disorders.

Chromosome studies[edit]

Schematickaryogramof a human, with annotatedbands and sub-bandsas used in theInternational System for Human Cytogenomic Nomenclatureforchromosomal abnormalities.It shows dark and white regions onG banding.It shows 22homologous chromosomes,both the male (XY) and female (XX) versions of thesex chromosome(bottom right), as well as themitochondrial genome(at bottom left).
Further information:Karyotype

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 akaryotypeinvolves 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 ofring 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 hybridizationis 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 ~200kbbacterial artificial chromosomesto 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[edit]

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, thenewborn screenincorporates biochemical tests to screen for treatable conditions such asgalactosemiaandphenylketonuria(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 byliquid chromatographyto 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 ofdisorders of amino acid metabolismsuch asurea cycle disorders,maple syrup urine disease,andPKU.Measurement of amino acids in urine can be useful in the diagnosis ofcystinuriaor renalFanconi syndromeas can be seen incystinosis.
  • 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 abnormalorganic acids.These compounds are normally produced during bodily metabolism of amino acids and odd-chain fatty acids, but accumulate in patients with certainmetabolic 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, includingMCAD.
  • Pyruvate and lactate are byproducts of normal metabolism, particularly duringanaerobic metabolism.These compounds normally accumulate during exercise or ischemia, but are also elevated in patients with disorders of pyruvate metabolism or mitochondrial disorders.
  • Ammoniais an end product of amino acid metabolism and is converted in the liver toureathrough a series of enzymatic reactions termed theurea cycle.Elevated ammonia can therefore be detected in patients withurea cycle disorders,as well as other conditions involvingliver failure.
  • Enzyme testing is performed for a wide range of metabolic disorders to confirm a diagnosis suspected based on screening tests.

Molecular studies[edit]

Treatments[edit]

Each cell of the body contains the hereditary information (DNA) wrapped up in structures calledchromosomes.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, particularlyinborn 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 therapyis used to replace the missing enzyme. Current research is actively seeking to usegene therapyor other new medications to treat specific genetic disorders.

Management of metabolic disorders[edit]

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, includinggalactosemia,phenylketonuria(PKU),maple syrup urine disease,organic acidurias andurea 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 ofpyridoxine(vitamin B6) in some patients withhomocystinuriato boost the activity of the residual cystathione synthase enzyme, administration ofbiotinto restore activity of several enzymes affected by deficiency ofbiotinidase,treatment withNTBCinTyrosinemiato inhibit the production of succinylacetone which causes liver toxicity, and the use ofsodium benzoateto decreaseammoniabuild-up inurea cycle disorders.

Certainlysosomal storage diseasesare treated with infusions of a recombinant enzyme (produced in a laboratory), which can reduce the accumulation of the compounds in various tissues. Examples includeGaucher disease,Fabry disease,MucopolysaccharidosesandGlycogen storage disease type II.Such treatments are limited by the ability of the enzyme to reach the affected areas (theblood brain barrierprevents 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[edit]

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

Career paths and training[edit]

Geneticist working with a pedigree

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 theAmerican Board of Medical Genetics.

Career Degree Description Training
Clinical geneticist MBBS,MD,DO,orMD-PhD A 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 adifferential 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.[citation needed]
Genetic counselor MS Agenetic counselorspecializes in communication of genetic information to patients and families. Genetic counselors often work closely with Clinical geneticists or other physicians (such asObstetriciansorOncologists) and often convey the results of the recommended tests. College (4 yrs) → Graduate program in Genetic counseling (2 yrs).
Metabolic nurse and/or nutritionist BA/BS, MS, RN One 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 diagnostics BS, MS, PhD, MBBS, MD, DO, MD-PhD Individuals who specialize inBiochemical geneticstypically work in the diagnostic laboratory, analyzing and interpreting specializedbiochemicaltests that measureamino acids,organic acids,andenzymeactivity. 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 diagnostics BS, MS, PhD, MBBS, MD, DO, MD-PhD Individuals who specialize inCytogeneticstypically work in the diagnostic laboratory, analyzing and interpretingkaryotypes,FISH,andcomparative genomic hybridizationtests. 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 genetics BS, MS, PhD, MBBS, MD, DO, MD-PhD Individuals who specialize inMolecular geneticstypically work in the diagnostic laboratory, analyzing and interpreting specialized genetic tests that look for disease-causing changes (mutations) in theDNA.Some examples of molecular diagnostic tests includeDNA sequencingandSouthern blotting. College (4 yrs) → Graduate school (PhD, usually 4–7 years) and/or Medical school (4 years)
Research geneticist BS, MS, PhD, MBBS, MD, DO, MD-PhD Any 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 technician AS, BS, MS Technicians 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[edit]

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 ofCRISPRandzinc finger,to edit thehuman genomein a way that can be inherited.[7][8][9][10]In April 2015 and April 2016, Chinese researchersreportedresults ofbasic researchto edit theDNAof non-viablehuman embryosusing CRISPR.[11][12][13]In February 2016, British scientists were given permission by regulators to genetically modifyhuman embryosby using CRISPR and related techniques on condition that the embryos were destroyed within seven days.[14]In June 2016 the Dutch government was reported to be planning to follow suit with similar regulations which would specify a 14-day limit.[15]

Societies[edit]

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

InAustraliaandNew Zealand,medical geneticists are trained and certified under the auspices of theRoyal Australasian College of Physicians,but professionally belong to theHuman Genetics Society of Australasiaand its special interest group, theAustralasian Association of Clinical Geneticists,for ongoing education, networking and advocacy.

bioethics[edit]

[16]

Research[edit]

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 ofgenetic testing

Basic genetics research[edit]

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

Allelic architecture of disease[edit]

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.[17][18][19]According to thecommon disease/common varianthypothesis, 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[edit]

Further information:Population structure (genetics)

One area in which population categories can be important considerations in genetics research is in controlling for confounding betweenpopulation 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,[32]although the magnitude of this problem in genetic association studies is subject to debate.[33][34]Various methods have been developed to detect and account for population substructure,[35][36]but these methods can be difficult to apply in practice.[37]

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[edit]

References[edit]

  1. ^"American Board of Medical Genetics and Genomics".abmgg.org.
  2. ^"Training Options - ABMGG".abmgg.org.
  3. ^RACP."Clinical Genetics".Royal Australasian College of Physicians.
  4. ^Resta, Robert (19 May 2006)."A new definition of genetic counseling: national society of genetic counselors' task force report".Journal of Genetic Counseling.15(2): 77–83.doi:10.1007/s10897-005-9014-3.PMID16761103.S2CID25809385.
  5. ^Rose, Nikolas. (2009).The Politics of Life Itself: Biomedicine, Power, and Subjectivity in the Twenty-First Century.Princeton University Press.ISBN978-0-691-12190-1.OCLC995257497.
  6. ^KOCH, TOM (2011-03-25)."Eugenics and the Genetic Challenge, Again: All Dressed Up and Just Everywhere to Go".Cambridge Quarterly of Healthcare Ethics.20(2): 191–203.doi:10.1017/s0963180110000848.ISSN0963-1801.PMC3535762.PMID21435294.
  7. ^Wade, Nicholas (19 March 2015)."Scientists Seek Ban on Method of Editing the Human Genome".New York Times.Retrieved20 March2015.
  8. ^Pollack, Andrew (3 March 2015)."A Powerful New Way to Edit DNA".New York Times.Retrieved20 March2015.
  9. ^Baltimore, David; Berg, Paul; Botchan, Dana; Charo, R. Alta; Church, George; Corn, Jacob E.; Daley, George Q.; Doudna, Jennifer A.; Fenner, Marsha; Greely, Henry T.; Jinek, Martin; Martin, G. Steven; Penhoet, Edward; Puck, Jennifer; Sternberg, Samuel H.; Weissman, Jonathan S.; Yamamoto, Keith R. (19 March 2015)."A prudent path forward for genomic engineering and germline gene modification".Science.348(6230): 36–8.Bibcode:2015Sci...348...36B.doi:10.1126/science.aab1028.PMC4394183.PMID25791083.
  10. ^Lanphier, Edward; Urnov, Fyodor; Haecker, Sarah Ehlen; Werner, Michael; Smolenski, Joanna (26 March 2015)."Don't edit the human germ line".Nature.519(7544): 410–411.Bibcode:2015Natur.519..410L.doi:10.1038/519410a.PMID25810189.
  11. ^Kolata, Gina (23 April 2015)."Chinese Scientists Edit Genes of Human Embryos, Raising Concerns".New York Times.Retrieved24 April2015.
  12. ^Liang, Puping; Xu, Yanwen; Zhang, Xiya; Ding, Chenhui; Huang, Rui; Zhang, Zhen; Lv, Jie; Xie, Xiaowei; Chen, Yuxi; Li, Yujing; Sun, Ying; Bai, Yaofu; Songyang, Zhou; Ma, Wenbin; Zhou, Canquan; Huang, Junjiu (18 April 2015)."CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes".Protein & Cell.6(5): 363–72.doi:10.1007/s13238-015-0153-5.PMC4417674.PMID25894090.
  13. ^Regalado, Antonio (2016-05-08)."Chinese Researchers Experiment with Making HIV-Proof Embryos".MIT Technology Review.Retrieved2016-06-10.
  14. ^Gallagher, James (1 February 2016)."Scientists get 'gene editing' go-ahead".BBC News.BBC.Retrieved10 June2016.
  15. ^Amjad, Anneesa (2016-06-06)."Dutch government seeks to allow creation of human embryos for research".BioNews.Retrieved2016-06-10.
  16. ^D. Bonneau, S. Marlin, D. Sanlaville, J.-M. Dupont, H. Sobol, M. Gonzales, M. Le Merrer, P. Malzac, F. Razavi, S. Manouvrier, S. Odent, D. Stoppa-Lyonnet, Les tests génétiques à l’heure de la deuxième révision des lois de bioéthique, Pathologie Biologie, Volume 58, Issue 5, 2010, Pages 396-401
  17. ^Reich DA, Lander ES (2001). "On the allelic spectrum of human disease".Trends Genet.17(9): 502–510.doi:10.1016/s0168-9525(01)02410-6.PMID11525833.
  18. ^abPritchard JK(2002)."The allelic architecture of human disease genes: common disease-common variant...or not?".Hum Mol Genet.11(20): 2417–2423.doi:10.1093/hmg/11.20.2417.PMID12351577.
  19. ^Smith DJ, Lusis AJ (2002). "The allelic structure of common disease".Hum Mol Genet.11(20): 2455–2461.CiteSeerX10.1.1.497.3708.doi:10.1093/hmg/11.20.2455.PMID12351581.
  20. ^Goldstein DB, Chikhi L (2002). "Human migrations and population structure: what we know and why it matters".Annu Rev Genom Hum Genet.3:129–152.doi:10.1146/annurev.genom.3.022502.103200.PMID12142358.
  21. ^Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003). "Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease".Nat Genet.33(2): 177–182.doi:10.1038/ng1071.PMID12524541.S2CID6850292.
  22. ^abWeiss KM, Terwilliger JD (2000). "How many diseases does it take to map a gene with SNPs?".Nat Genet.26(2): 151–157.doi:10.1038/79866.PMID11017069.S2CID685795.
  23. ^Cardon LR, Abecasis GR (2003). "Using haplotype blocks to map human complex trait loci".Trends Genet.19(3): 135–140.CiteSeerX10.1.1.398.8937.doi:10.1016/s0168-9525(03)00022-2.PMID12615007.
  24. ^abKittles RA, Weiss KM (2003). "Race, ancestry, and genes: implications for defining disease risk".Annu Rev Genom Hum Genet.4:33–67.doi:10.1146/annurev.genom.4.070802.110356.PMID14527296.
  25. ^Pritchard JK(2001)."Are rare variants responsible for susceptibility to complex diseases?".Am J Hum Genet.69(1): 124–137.doi:10.1086/321272.PMC1226027.PMID11404818.
  26. ^Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs HH (2004). "Multiple rare alleles contribute to low plasma levels of HDL cholesterol".Science.305(5685): 869–872.Bibcode:2004Sci...305..869C.doi:10.1126/science.1099870.PMID15297675.S2CID39429794.
  27. ^Risch N, Burchard E, Ziv E, Tang H, "Categorization of humans in biomedical research: genes, race and disease",Genome Biol(2002) 3 (http://genomebiology /2002/3/7/comment/2007Archived2006-06-24 at theWayback Machine) (electronically published July 1, 2002; accessed August 25, 2005)
  28. ^Risch N (2000). "Searching for the genetic determinants in a new millennium".Nature.405(6788): 847–856.doi:10.1038/35015718.PMID10866211.S2CID4392356.
  29. ^Altmüller J, Palmer LJ, Fischer G, Scherb H, Wjst M (2001)."Genomewide scans of complex human diseases: true linkage is hard to find".Am J Hum Genet.69(5): 936–950.doi:10.1086/324069.PMC1274370.PMID11565063.
  30. ^Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K (2002)."A comprehensive review of genetic association studies".Genet Med.4(2): 45–61.doi:10.1097/00125817-200203000-00002.PMID11882781.
  31. ^Cooper RS, "Genetic factors in ethnic disparities in health", in Anderson NB, Bulatao RA, Cohen B, eds.,Critical perspectives on racial and ethnic differences in health in later life,(Washington DC: National Academy Press, 2004), 267–309.
  32. ^Cardon LR, Palmer LJ (2003). "Population stratification and spurious allelic association".Lancet.361(9357): 598–604.doi:10.1016/s0140-6736(03)12520-2.PMID12598158.S2CID14255234.;Marchini J, Cardon LR, Phillips MS, Donnelly P (2004)."The effects of human population structure on large genetic association studies".Nat Genet.36(5): 512–517.doi:10.1038/ng1337.PMID15052271.
  33. ^Thomas DC, Witte JS (2002). "Point: population stratification: a problem for case-control studies of candidate-gene associations?".Cancer Epidemiol Biomarkers Prev.11(6): 505–512.PMID12050090.
  34. ^Wacholder S, Rothman N, Caporaso N (2002). "Counterpoint: bias from population stratification is not a major threat to the validity of conclusions from epidemiological studies of common polymorphisms and cancer".Cancer Epidemiol Biomarkers Prev.11(6): 513–520.PMID12050091.
  35. ^Morton NE, Collins A (1998)."Tests and estimates of allelic association in complex inheritance".Proc Natl Acad Sci USA.95(19): 11389–11393.Bibcode:1998PNAS...9511389M.doi:10.1073/pnas.95.19.11389.PMC21652.PMID9736746.
  36. ^Hoggart CJ, Parra EJ, Shriver MD, Bonilla C, Kittles RA, Clayton DG, McKeigue PM (2003)."Control of confounding of genetic associations in stratified populations".Am J Hum Genet.72(6): 1492–1504.doi:10.1086/375613.PMC1180309.PMID12817591.
  37. ^Freedman ML, Reich D, Penney KL, McDonald GJ, Mignault AA, Patterson N, Gabriel SB, Topol EJ, Smoller JW, Pato CN, Pato MT, Petryshen TL, Kolonel LN, Lander ES, Sklar P, Henderson B, Hirschhorn JN, Altshuler D (2004)."Assessing the impact of population stratification on genetic association studies".Nat Genet.36(4): 388–393.doi:10.1038/ng1333.PMID15052270.
  38. ^Tian C, Gregersen PK, Seldin MF (October 2008)."Accounting for ancestry: population substructure and genome-wide association studies".Human Molecular Genetics.17(R2): R143–R150.doi:10.1093/hmg/ddn268.PMC2782357.PMID18852203.
  39. ^Hoggart CJ, Shriver MD, Kittles RA, Clayton DG, McKeigue PM (2004)."Design and analysis of admixture mapping studies".Am J Hum Genet.74(5): 965–978.doi:10.1086/420855.PMC1181989.PMID15088268.
  40. ^Patterson N, Hattangadi N, Lane B, Lohmueller KE, Hafler DA, Oksenberg JR, Hauser SL, Smith MW, O'Brien SJ, Altshuler D, Daly MJ, Reich D (2004)."Methods for high-density admixture mapping of disease genes".Am J Hum Genet.74(5): 979–1000.doi:10.1086/420871.PMC1181990.PMID15088269.
  41. ^Smith MW, Patterson N, Lautenberger JA, Truelove AL, McDonald GJ, Waliszewska A, Kessing BD, et al. (2004)."A high-density admixture map for disease gene discovery in African Americans".Am J Hum Genet.74(5): 1001–1013.doi:10.1086/420856.PMC1181963.PMID15088270.
  42. ^McKeigue PM (2005)."Prospects for admixture mapping of complex traits".Am J Hum Genet.76(1): 1–7.doi:10.1086/426949.PMC1196412.PMID15540159.
  43. ^Chaturvedi N (2001)."Ethnicity as an epidemiological determinant—crudely racist or crucially important?".Int J Epidemiol.30(5): 925–927.doi:10.1093/ije/30.5.925.PMID11689494.
  44. ^Collins FS, Green ED, Guttmacher AE, Guyer MS, US National Human Genome Research Institute (2003)."A vision for the future of genomics research".Nature.422(6934): 835–847.Bibcode:2003Natur.422..835C.doi:10.1038/nature01626.PMID12695777.S2CID205209730.

Further reading[edit]

External links[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Medical_genetics&oldid=1220254657"