Analisis Urutan Nukleotida Daerah Hipervariabel I (Hvi) Dna Mitokondria Untuk Menentukan Motif Populasi Suku Sunda

Sifat-sifat spesifik D-loop mtDNA dapat digunakan untuk menentukan identitas seseorang atau etnis tertentu. Suku Sunda merupakan salah satu etnis di Indonesia yang mengalami missing link dalam sejarah. Hal ini dikarenakan kurangnya peninggalan sejarah dan belum adanya penelitian yang secara khusus meneliti suku Sunda asli. Beberapa wilayah yang masih mempertahankan budaya Sunda yaitu kampung Baduy, Ciptagelar, Kuta, dan Dukuh. Penelitian ini bertujuan untuk menentukan analisis urutan nukleotida daerah hipervariabel I (HVI) D-loop mtDNA pada dua puluh manusia suku Sunda dari keempat wilayah tersebut (lima sampel mtDNA dari setiap wilayah). Analisis homologi dilakukan dengan membandingkan urutan nukleotida seluruh sampel dengan Cambridge, manusia Indonesia di Gene Bank. Hasil Homologi urutan nukleotida dua puluh manusia suku Sunda ditemukan 42 varian, enam diantaranya merupakan varian baru, yaitu t(16045)A, g(16118)A, a(16177)C, g(16110)C, g(16156)C dan c(16365)-. Tingkat homologi urutan nukleotida di antara kedua puluh sampel manusia suku Sunda, berkisar antara 91,5–100%. Dari analisis pohon filogenetik didapatkan dua haplotip, yaitu haplotip tac dan taT. Adanya haplotip asli (tac) dan taT pada sampel masyarakat suku Sunda mengindikasikan bahwa nenek moyang suku Sunda yang membawa haplotip tac telah menempati kepulauan Indonesia yang selanjutnya mengalami evolusi dengan menghasilkan mutasi baru pada posisi 16261 membentuk haplotip taT serta ditunjukkan beberapa individu dari kampung Kuta merupakan individu yang tertua yang kemudian berevolusi dan bermigrasi dari haplotip tac menjadi taT. Hasil penelitian ini diharapkan dapat melengkapi data base varian normal mtDNA manusia Indonesia

Variability of major histocompatibility complex class II genes in the golden jackals (Canis aureus) from Israel

Geni glavnog sustava tkivne podudarnosti (MHC) ključna su komponenta imunološkog sustava kod sisavaca te su i važan molekularni marker adaptivne genetičke raznolikosti u divljim populacijama životinja. Veća raznolikost MHC gena unutar populacije povećava izglede populacije za obranu od patogena i parazita, a time i izglede za dugoročno preživljavanje. Čagalj (Canis aureus) pripada porodici Canidae (psi), podred Caniformia, redu Carnivora (mesojedi). Do sada nema objavljenih istraživanja raznolikosti MHC gena ove vrste. Cilj ovog diplomskog rada je odrediti razinu raznolikosti DQA, DQB i DRB gena skupine II MHC sustava u čagljeva iz Izraela. Iz 30 uzoraka uške čaglja, postupcima izolacije DNA, PCR metodom, elektroforezom, sekvenciranjem i molekularnim kloniranjem, pronađena su tri alela na DQA lokusu, pet alela na DQB lokusu i četiri alela na DRB lokusu. Našli smo jedan novi jedinstveni alel na DRB lokusu (DRB1*04802var). Ostali pronađeni aleli poznati su iz prethodnih istraživanja na ostalim vrstama porodice pasa, što potvrđuje postojanje trans-specijskog polimorfizma. DQB i DRB lokusi pokazuju veliku raznolikost alela i velike evolucijske udaljenosti te visok omjer nesinonimnih supstitucija naspram sinonimnih, što potvrđuje pretpostavku djelovanja pozitivne selekcije na te lokuse.The genes of major histocompatibility (MHC) system are a key component of the immune system in mammals and are important molecular markers of adaptive genetic diversity in wild animal populations. Greater diversity of MHC genes within the population increases the chances of defence against pathogens and parasites, and thus the prospects for long-term survival. Golden jackal (Canis aureus) belongs to the family Canidae (dogs), suborder Caniformia, order Carnivora (carnivores). So far there are no published studies of MHC gene diversity on this species. The aim of this graduate thesis is to determine the level of diversity of the MHC system class II DQA, DQB and DRB genes in golden jackals from Israel. Three alleles at DQA locus, five alleles at DQB locus and four alleles at the DRB locus were found in 30 samples of jackal's ear. Methods used were DNA isolation, PCR method, electrophoresis, sequencing and molecular cloning. We found one new unique allele on DRB locus (DRB1*04802var). The rest of the alleles found are known from previous research on the other species of the dog family, which confirms the existance of a trans-species polymorphism. DQB and DRB loci show great diversity of alleles, large evolutionary distances, high ratio of non-synonymous versus synonymous substitutions, confirming the assumption that loci are influenced by positive selection

Polymorphism of HLA-DRB4 gene in Croatia

U ovom istraživanju analiziran je polimorfizam gena HLA-DRB4 i haplotipova HLA-DRB1-DRB4 u Hrvatskoj među kadaveričnim davateljima organa (N=144). Svi uzorci bili su odabrani na temelju prisustva jednog od alela skupine HLA-DRB53 (aleli DRB1*04, DRB1*07 i DRB1*09). Određivanje alela lokusa HLA-DRB4 provedeno je metodom lančane reakcije polimerazom i početnicama specifičnim za jedan ili više alela HLA (engl. Polymerase Chain Reaction–Sequence Specific Primers, PCR-SSP). Aleli lokusa HLA-DRB1 i -DQB1 određeni su metodom lančane reakcije polimerazom i probama specifičnim za jedan ili grupu alela HLA (engl. Polymerase Chain Reaction–Sequence Specific Oligos, PCR-SSO). Na lokusu HLA-DRB4 otkriveno je sedam različitih alela, 5 funkcionalnih alela (DRB4*01:01:01:01, DRB4*01:02, DRB4*01:03, DRB4*01:05 i DRB4*01:08) i dva nul alela (DRB4*01:03:01:02N i HLA-DRB4*03:01N). Među ispitanicim pozitivnim za jedan od alela skupine HLA-DRB1*04 nije otkrivena statistički značajna razlika u raspodjeli alela DRB4 s obzirom na prisustvo alela DQB1. U haplotipovima HLA-DRB1*04-DQB1 najčešći prisutni alel je bio DRB4*01:03 (86,7%). Među HLA-DRB1*07:01 pozitivnim haplotipovima uočena je statistički značajna razlika (p<0,05) u raspodjeli alela HLA-DRB4 s obziroma na prisustvo alela HLA-DQB1. Haplotipovi: HLA-DRB1*07:01-DQB1*03:03 na lokusu HLA-DRB4 u 98,0% slučajeva imali su nul alel DRB4*01:03:01:02N, dok su haplotipovi DRB1*07:01-DQB1*02:02 na lokusu DRB4 u 65,5% slučajeva imali prisutan alel DRB4*01:03. Unutar skupine HLA-DRB1*04 pozitivnih haplotipova nije uočena statistički značajna razlika u raspodjeli alela HLA-DRB4 s obzirom na prisustvo alela HLA-DQB1. Alel HLA-DRB1*09:01 je kod svih ispitanika uočen u kombinaciji s alelima HLA-DRB4*01:03-DQB1*03:03.In this study the polymorphism of HLA-DRB4 alleles and HLA-DRB1-DRB4 haplotypes among Croatian cadaveric organ donors (N = 144) was analyzed. All samples were selected based on the presence of one of the alleles of HLA-DRB53 group (DRB1*04, DRB1*07, and DRB1*09 alleles). Typing of HLA-DRB4 alleles was carried out by polymerase chain reaction sequence specific primers for one or more HLA alleles (method: PCR-SSP). HLA-DRB1 and -DQB1 alleles were determined by polymerase chain reaction sequence specific oligos for one allele or a group of HLA alleles (method: PCR-SSO). On the HLA-DRB4 locus seven different alleles were discovered; 5 functional alleles (DRB4*01:01:01:01, DRB4*01:02, DRB4*01:03, DRB4*01:05, and DRB4*01:08) and two null alleles (DRB4*01:03:01:02N and HLA-DRB4*03:01N). Among individuals positive for one of the HLA-DRB1*04 alleles no statistically significant difference was detected in the distribution of the HLA-DRB4 alleles given the presence of the DQB1 alleles. Among HLA-DRB1*04-DQB1 haplotypes the most present was DRB4*01:03 allele (86.7%). Among HLA-DRB1*07:01 positive haplotypes a statistically significant difference (p<0.05) in the distribution of HLA-DRB4 alleles due to the presence of different HLA-DQB1 alleles was observed. The HLA-DRB1*07:01-DQB1*03:03 haplotype in 98.0% of cases had the DRB4*01:03:01:02N allele on the HLA-DRB4 locus, while DRB1*07:01-DQB1*02:02 haplotype on the HLA-DRB4 locus in 65.5% of cases had the DRB4*01:03 allele (65.5%). Within the group of the HLA-DRB1*04 positive haplotype, there was no statistically significant difference in the distribution of HLA-DRB4 alleles due to the presence of different HLA-DQB1 alleles. The HLA-DRB1*09:01 allele was observed in combination: HLA-DRB4*01:03-DQB1*03:03 in all the cases

Influència de l'haplotip 46/1 del gen JAK2 en la variació de la càrrega al·lèlica de la mutació JAK2V617F en pacients amb policitèmia vera i trombocitèmia esencial

La presència de l'haplotip 46/1 del gen JAK2 predisposa a neoplàsies mieloproliferatives associades a la mutació de JAK2V617F, però la seva rellevància clínica és desconeguda. En aquest treball determinem, de forma retrospectiva, la càrrega al·lèlica de JAK2V617F de 62 pacients amb NMP JAK2V617+, en el moment del diagnòstic i en l'últim control. Posteriorment, analizem l'augment de la càrrega al·lèlica de JAK2V617F amb l'objectiu de determinar si aquesta es manté estable o presenta un augment progressiu durant el curs natural de la malaltia. Finalment, analitzem la relació entre els resultats obtinguts i l'evolució clínica dels pacients

Molecular Phylogenetics and Population Structure of two Mahseer Species (Tor Tambroides Bleeker and Tor Douronensis Valenciennes: Cyprinidae) in Malaysia

This study examines the phylogenetic relationships of mahseer (genus Tor and Neolisssochillus) and their relationships with other selected cyprinids using sequence analysis of mitochondrial DNA cytochrome c oxidase I (COI) gene (464 base pairs). This study also describes the genetic structure of Tor tambroides and Tor douronensis, two important mahseer in Malaysia using both mitochondrial COI sequences and nuclear microsatellites DNA. The findings of the phylogenetic study strongly support the reciprocally monophyletic status between genus Tor (T. douronensis and T. tambroides) and genus Neolissochillus (represented by Neolissochillus stracheyi.) thus, strengthen the taxonomic status for all the three indigenous mahseer. For the other indigenous cyprinids, an interesting finding was that Barbonymus gonionotus was phylogenetically distinct from its morphologically similar species, Barbonymus schwanenfeldii (K2P distance value = 15.1%), and did not group together in a single Barbonymus clade. The population structure analysis inferred from mitochondrial COI sequences found high levels of intra and inter-population variations in T. douronensis. The presence of fixed haplotype differences among the populations, along with high FST values indicated that there has been little or no migration occur among the extant populations separated by large geographic distances, or river systems. For T. tambroides, low level of mitochondrial variations was found among the populations. The reason is probably due to the high proportion of the HKE1 haplotype found in most populations (0.736-1.000) studied except from Endau-Rompin (HKE4 is the dominant haplotype), or by the small number of samples used in the present study

Applicability of MHC loci as markers for detecting hybridization between wolf (Canis lupus) and dog (Canis lupus familiaris)

Vukovi su česta pojava u blizini ljudskih naselja, koja naseljavaju i psi. Sve vrste roda Canis mogu stvarati plodno potomstvo, što znači da i vukovi i psi mogu stvarati hibride. Hibridizacija između divljih i udomaćenih vrsta, iako može imati i pozitivne posljedice, uglavnom se percipira kao prijetnja bioraznolikosti, najviše zbog introgresije alela domesticiranih vrsta, koji su nastali umjetnom selekcijom, u divlje populacije. Hibridi se ne mogu pouzdano identificirati samo po morfološkim obilježjima nego se koriste i molekularne metode. Uz uobičajenu genetičku analizu mitohondrijske DNA, Y kromosoma i mikrosatelita, 2012. godine prvi put je uspješno upotrijebljena analiza MHC lokusa kao metoda otkrivanja hibridizacije. U svrhu provjere primjenjivosti ove metode na hibride između vukova i pasa analizirani su aleli i haplotipovi DRB, DQA i DQB lokusa glavnog sustava tkivne podudarnosti 13 potencijalnih hibrida od kojih su tri bila ranije potvrđena kao hibridi nastali povratnim križanjem s vukom, i uspoređeni s podacima dobivenim za vuka i psa iz literature. U dva uzorka MHC lokusi nisu se pokazali informativnima za otkrivanje hibridizacije, dok su za jedan uzorak bili informativni. MHC lokusi mogu biti dobri biljezi za otkrivanje hibridizacije vuka i psa jedino u slučaju kad potecijalni hibridi nose privatne alele za pojedinu vrstu.Wolves can often be seen near human settlements, where dogs live. All Canis species are closely related and can produce fertile progeny. Hybridization between wild and domesticated species can have a positive outcome, but it is usually percieved as threat to biodiversity, mostily because of the possibility of introgression of artificially selected domestic alleles into wild populations. Hybrids can't be identified solely based on morphological features, so using molecular methods is necessary. In 2012, along with the usual analysis of the mithochondrial DNA, Y chromosome and microsatellites, MHC loci analysis was used to detect hybrids for the first time. In order to find out if this method is applicable in detecting wolf-dog hybrids, DRB, DQA, DQB alleles and haplotypes of 13 suspected hybrids, three of which were earlier confirmed as back – crosses with wolves, were analysed and compared to available data from existing literature. MHC loci were informative in detecting hybridization for one of those samples, but weren't for other two. MHC loci are effective markers only when potential hybrids are carrying private alleles for each species

Molecular markers in identification of oyster species in the Adriatic Sea

Školjkaš Crassostrea gigas (Thunberg 1793) prirodno je rasprostranjen na obalama Japana te jugoistočne Azije. Ova vrsta uvedena je na područje Europe 1960-tih godina kako bi zamijenila izlovljene populacije autohtone vrste Ostrea edulis (Linnaeus 1758). Vrsta O. edulis je gospodarski vrlo važan školjkaš široko prisutan u Jadranu, dok je vrsta C. gigas u hrvatski dio Jadrana unesena relativno nedavno. Isključivo morfološko razlikovanje vrsta O. edulis i C. gigas može biti nepouzdano. Stoga su u ovom radu korišteni mitohondrijski biljezi 16S rDNA i COI kako bi se potvrdila prisutnost alohtone vrste C. gigas u području sjevernog Jadrana kao i njezino širenje u područje srednjeg Jadrana. Ovim radom dokazano je također da se nuklearni biljezi 5S rDNA, ITS1 i ITS2 mogu koristiti u svrhu uspješnog razlikovanja jedinki vrsta C. gigas i O. edulis.The clam Crassostrea gigas (Thunberg 1793) is a native species on the coast of Japan and Southeast Asia. C. gigas was introduced into European coastal waters in the 1960’s in an attempt to replace the overexploited populations of the native clam Ostrea edulis (Linnaeus 1758). The species O. edulis is economically very important and is widely present on the coast of the Adriatic sea, while the species C. gigas has been recently introduced onto the Croatian coast of the Adriatic. Discrimination between species O. edulis and C. gigas based only on morphology can be unreliable. Therefore the mitochondrial markers 16S rDNA and COI were used to confirm the presence of the invasive species C. gigas in the northern Adriatic as well as its propagation to the central Adriatic. Furthermore this thesis proved that nuclear markers 5S rDNA, ITS1 and ITS2 can be used for successful differentiation between the species C. gigas and O. edulis

Variability of major histocompatibility complex class II DQA/DQB/DRB haplotypes in the golden jackal (Canis aureus) from Serbia

Glavni sustav tkivne podudarnosti (MHC) sudjeluje u adaptivnom imunosnom odgovoru sisavaca. Veća raznolikost gena MHC omogućuje limfocitima T da prepoznaju širi spektar antigena, što u konačnici daje jedinci, ali i populaciji veću šansu za preživljavanje napada patogena. Dobar su molekularni marker za proučavanje genetičke raznolikosti vrsta i populacija zbog svoje poligenosti i polimorfnosti. Čagalj (Canis aureus) je zvijer (red Carnivora) koja pripada porodici pasa (Canidae). Istraživanja raznolikosti gena MHC kod čaglja tek su nedavno započela unatoč njegovoj širokoj rasprostranjenosti na euroazijskom i afričkom kontinentu. Cilj ovog istraživanja je određivanje raznolikosti tro-lokusnih haplotipova DQA/DQB/DRB te pojedinih lokusa skupine II sustava MHC u populaciji čagljeva iz Srbije. U ovom istraživanju na 29 uzoraka mišića čagljeva pronađeno je tri alela lokusa DQA i DQB, četiri alela lokusa DRB te šest haplotipova. Sedam je alela dosad pronađeno samo kod čaglja, a tri su trans-specijski polimorfizmi. Tri su haplotipa pronađena samo u srpskoj populaciji, a tri haplotipa su zajednička s istočnoeuropskom populacijom. Potvrđena je postavljena hipoteza djelovanja pozitivne selekcije na svim lokusima koristeći dN/dS test, odnosno omjer nesinonimnih i sinonsimnih supstitucija na nukleotidnom slijedu alela.The genes of the major histocompatibility (MHC) system takes part in the adaptive immune response in mammals. Greater diversity of MHC genes enables T lymphocytes to recognise a wider spectrum of antigens, which in turn gives the individual a greater chance of surviving a pathogen attack. They are a good molecular marker for studying genetic diversity of both species and populations because they are polygenic and polymorphic. The golden jackal (Canis aureus) is a carnivore from the dog family (Canidae). Studies of MHC gene diversity of golden jackals have only recently emerged despite its wide distribution on the Eurasian and African continent. The aim of this graduate thesis is to determine variability of three-locus DQA/DQB/DRB haplotypes and individual Class II MHC loci in golden jackals from Serbia. In this study of 29 jackal muscle samples we have found three DQA and DQB alleles, four DRB alleles and six haplotypes. Seven alleles have only been found in jackals so far, while three alleles are trans-species polymorphisms. Three haplotypes are private to the serbian populations, while three haplotypes are shared with the Eastern European population. We have confirmed the proposed hypothesis of existing positive selection on all loci using the dN/dS test, i.e. the ratio of non-synonymous and synonymous substitutions on the allelic nucleotide sequences

Türkiye'deki Mezopotamya dikenli yılan balığının (Mastacembelus mastacembelus) (Teleostei: Synbranchiformes) populasyon yapısı ve moleküler filogenisi

The Mesopotamian spiny eel Mastacembelus mastacembelus is an endemic freshwater fish confined to the Euphrates and Tigris drainages of Mesopotamia. In this study, it was aimed to reveal the genetic variation of Mesopotamian spiny eel in Turkey with samples from the distribution regions in the Tigris and Euphrates river basins. For this purpose, the partial mitochondrial COI gene region (656 bp) was sequenced from 15 samples from seven populations (Aksu, Merzimen, Karasu, Sinnep, Ambar, Zarova streams and main body of Tigris River). Eight variable nucleotide positions were identified and three of which were polymorphic. Overall haplotype and nucleotide diversity are Hd= 0.642±0.081 and π=0.00339±0.00069. Four haplotypes were identified, one from the Tigris River basin, and three from the Euphrates River basin. Haplotype network analysis contains four unique haplotypes with at least one mutational step and no haplotype shared between main river drainages. The most common haplotype was H1 and three Tigris populations shared it. The phylogenetic inferences suggest that Mastacembelus populations are divided into two main clades. The first clade consists of haplotypes of the Tigris River basin while the second clade contains Euphrates River basin populations.Mezopotamya dikenli yılan balığı Mastacembelus mastacembelus, Mezopotamya'nın Fırat ve Dicle nehri drenajlarıyla sınırlı endemik bir tatlı su balığıdır. Bu çalışmada, Mezopotamya dikenli yılan balığının Türkiye'deki genetik varyasyonunun Dicle ve Fırat nehir havzalarındaki dağılım bölgelerinden örneklerle ortaya çıkarılması amaçlanmıştır. Bu amaçla, yedi popülasyondan (Aksu, Merzimen, Karasu, Sinnep, Ambar ve Zarova dereleri ve Dicle Nehri ana gövde) 15 örneğin kısmi mitokondiyal COI gen bölgesi (656 bç) sekanslanmıştır. Sekiz değişken mükleotit pozisyonu tespit edilmiş olup ve bunların üç tanesi polimorfik nükleotit olarak belirlenmiştir. Genel haplotip ve nükleotid çeşitliliği Hd= 0,642±0,081 ve π=0,00339±0,00069 olarak hesaplanmıştır. Biri Dicle Nehri Havzasından, üçü Fırat Nehri Havzasından olmak üzere dört haplotip tespit edilmiştir. Haplotip ağ analizinde en az bir mutasyon farkı olan ve ana nehir drenajları arasında haplotip paylaşımı olmayan dört haplotip belirlenmiştir. En yaygın haplotip H1 haplotipi olup ve üç Dicle popülasyonu tarafından paylaşılmaktadır. Filogenetik analizler sonucunda, Mastacembelus popülasyonlarının iki ana haplogruba ayrıldığı ortaya çıkarılmıştır. Birinci haplogrubu, Dicle Nehri havzası populasyonlarının, ikinci haplogrubu ise, Fırat Nehri havzası popülasyonlarının ve haplotiplerinin oluşturduğu belirlenmiştir

Pharmacogenetics – individualized treatment of genetic disorders

Farmakogenetika je grana znanosti koja proučava povezanost genotipa sa različitom reakcijom na terapiju nekim lijekovima. Potencijal farmakogenetike je velik jer će dobiveni rezultati istraživanja omogućiti i olakšati individualizirano liječenje. Tiopurin S-metiltransferaza (TPMT) je enzim koji inaktivira tiopurinske lijekove te sprječava njihov prelazak u toksične produkte. U genu za TPMT postoje polimorfizmi koji uzrokuju varijabilnu aktivnost enzima. Kod pacijenata koji su deficijentni za TPMT može doći do trovanja krvi i kod njih se doza tiopurinskih lijekova mora smanjiti. Četiri varijante polimorfnih alela za TPMT su najviše proučavane jer imaju najveći utjecaj na smanjenje aktivnosti TPMT-a: TPMT*2, TPMT*3A, TPMT*3B i TPMT*3C te čine 95% nasljedne deficijencije za enzim TPMT. Varfarin je oralni antikoagulans koji u stanici djeluje kao inhibitor vitamin K epoksid reduktaza kompleksa (podjedinice VKORC1). Varijabilni farmakogenetički odgovor ovisi o polimorfizmima dva enzima: CYP2C9 (enzim koji metabolizira lijek) i VKORC1. Najčešći varijantni aleli za CYPC9 su CYP2C9*2 i CYP2C9*3. Osoba koja ima te alele za najbolji učinak mora primati manju dozu lijeka. Varijante kompleksa VKORC1 se mogu podijeliti u 4 haplotipa: VKORC1*1, *2, *3 i *4. VKORC1*1 se uzima kao referenca, za haplotip VKORC1*2 potrebna je manja doza lijeka, a haplotipovi VKORC1*3 i VKORC1*4 trebaju veću dozu varfarina Serotoninski transporter (SERT) omogućuje ponovni ulazak serotonina u neurone. Gen za SERT sadrži polimorfizme koji utječu na njegovu ekspresiju i funkciju. SERT je cilj djelovanja nekih antidepresiva. Dosadašnja istraživanja su pokazala da zbog polimorfizama u promotorskoj regiji gena za SERT može doći do slabijeg reagiranja na terapiju antidepresivima, ali zbog postojanja kontradiktornih rezultata trenutno nije moguće na temelju genotipa odrediti optimalnu dozu lijeka.Pharmacogenetics is a branch of science that studies the association of genotype with individual response to drug therapy. The potential of pharmacogenetics is great because further research will enable and facilitate individualized treatment of some diseases. Tiopurin S-methyltransferase (TPMT) is an enzyme that inactivates thiopurine drugs and prevents their transformation to toxic products. The TPMT gene exhibits genetic polymorphisms that cause variable enzyme activity. TPMT deficient patients are at high risk of hematologic toxicity and should be treated with reduced dose of thiopurine drugs. Four polymorphic variant TPMT alleles have been most studied because they have the greatest impact on reducing activity of TPMT: TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C. Warfarin, an anticoagulant, acts as an antagonist of vitamin K epoxide reductase complex (VKORC1 subunit). Polymorphisms in CYP2C9 (metabolizes Warfarin) and VKORC1 cause variable patient response. The most common variant alleles for CYPC9 are CYP2C9*2 and CYP2C9*3. Patients with these alleles require a lower dose of drug. VKORC1 variants can be divided into four haplotypes: VKORC1 *1, *2, *3 and *4. VKORC1*1 is considered the reference, while patients with the VKORC1*2 require lower and patients with VKORC1*3 and VKORC1*4 higher warfarin doses. Serotonin transporter (SERT) is the transporter protein in charge of serotonin reuptake. SERT gene polymorphisms affect its expression and function. SERT is the target of some antidepressants. Some studies have shown that polymorphisms in the SERT gene promotor region cause poor response to antidepressants, but because of some conflicting results it is not possible yet to determine the optimal antidepressant dose based on genotype