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HUMANGENETICSDR. KAMAJAYA, MSc.,SpAnd.BAGIAN BIOLOGIFAKULTAS KEDOKTERAN U.S.U.MEDAN.MEDAN

G E N E T I C S DEFINISI. IlmuIlyang mempelajaril j i tentangsifat, karakter, penyakit atau cacatyang diturunkan dari orangorang-tuatuakepada turunan nya, dan caracara penurunannya.

SIFAT, KARAKTER,PENYAKIT, DAN CACATHEREDITER.HEREDITER Onset ? Tingkat abnormalitas genetik :1. Chromosomal,2. Genome.3. Molecular.

HUMAN CHROMOSOME.CHROMOSOME Normalm HumanmChromosomemm : Somatic cells 2n 46 chromosome22 pair of Autosome XX sex-chrom. sex chrom 22 pair of Autosome XY sex-chrom. Gametic cells n 23 chromosome22 Autosome X / Y sex-chromosome.

Human chromosomes. Abnormal human chromosomes :A AbA.Abnormall off chromosomehsett (aneuploidy)(l id ) :1.4n (92 chrom) Tetraploidy2 3 (69 chrom)2.3nh) TriploidyT i l id3. n (23 chrom) Haploidy (somatic-cell)B.Abnormal number of chromosome :1. 2n 2 (48 chrom) Tetrasomy,2. 2n 1 (47 chrom) Trisomy3. 2n - 1 (45 chrom) Monosomy

Human chromosomeC. Abnormal chromosome strukture.1. Defisient chromosome.2. Duplication.3. Translocation.4 I4.Inversion.i5. Fragil chromosome.

GENOMEA. Mendelian Inheritances.1 Monohybrid1.Monohybrid,2. Dihybrid,3. Trihybrid,4 Multihybrid4.Multihybrid.

Genome Non-Mendelian Inheritances.1 Inc1.Incomplitmplit DDominancy,min nc2. Intermedier Inheritances,3 Epistasis3.Epistasis,4. Multiple gene Inheritances,5. Multiplep alleles,6. Sex-differences :a. Sex Influenced Characters,b Sexb.S LimitedLi it d ChCharacters,tC. Sex Linked Characters.

M lMolecularl GeneticsGti BBasici strukturekoff DNA & RNA molecules,ll DNA – Replication. Reproductive and Syntesis replication, Central Dogma. Codon Operon theory (Jacob and Monod).

MENDELIAN INHERITANCES. A. Monohybrid.P. Black X White F2. BBbbG1.Bb F1.BbB(Black)G2.B-bbBbBBBbBlack BlackBbBbBlack WhiteF2.ratio Black : White 3 : 1.

B. Mendelian dihybridF2.P. Black-short X 2G2.BS – Bs – bS - bs BSBBsbSbbsBSBBSS BBSsBbSS BbssBsBBSsBbSsbSBbSS BbSsbbSS bbSsbbsBbSBbSsbbSbbSsBBssBbBbssBbssbbbbssF2. ratio Bl-sh : Bl-Lg : Wh-sh : Wh-lg 1 : 3 : 3 : 1.

NON-MENDELIAN INHERITANCES.1. Incomplite dominancy &2 Intermedier Inheritances2.F2.P. Red X WhiteRRWWG1.RWF1.RW(Orange) RWRRRRWWRW WWF2. ratio Red : Orange : White 1 : 2 : 1.

N n M nd li n InhNon-MendelianInheritances.it nF2.3. Epistasis (Deaf-mutism).P. Normal X NormalDdMmDdMmG1.DM-Dm-dM-dm DM Dm dM dm D DD DD Dd DdM MM Mm MM MmD DD DD Dd Ddm Mm mm Mm mmd Dd Dd dd ddF2.ratio Normal : Deaf-mute 9 : 7. M MM Mm MM Mmd Ddd Ddd dd ddm Mm mm Mm mm

Non Mendelian Inheritances.Non-MendelianInheritances4. Multiple gene Imheritance.L b h dariLebihdsepasang gen bekerjasamab k satu fenotip.C t h : a. Tinggi-badan,ContohTii b db. Warna-kulitc Hypertensic.H p t nsi herediter.hditd. Diabetes-mellitus herediter.Faktor lingkungan sangat berpengaruh Phenotype Genotype Environment.

Non-MendelianNonMendelian Inheritances.Inheritances5. Multiple alleles.ABO blood-groupsblood groupsa. ABO blood-groups.lP. A-Group het. X B-Group. Het.b. Rhesus-factor.Phenotype OIA – IOIB – IOF1. IA IBIOIOIAIB IBIOIAIO IOIO

Multiple alleles.Multiple-alleles.B. Rhesus-factor. Gol.darah Rhesus : Rhesus positif danRhesus negatif.negatif Frekwensi : - Ras Kaukasia Rh. 75-78%- RasR MongolMl Rh. Rh 98-99%98 99% Rhesus ppositif dominan thd Rhesus negatif.g

Rhesus-factor.G1.F1. Rh.pos.,het. X Rh.pos.het.RrRrR–rR-r RrRrRRRrRrrrF2-ratio :Rhesus pos. : Rhesus neg. 3:1

Antigen Rhesus : Wiener.Genotype Antigen rhesusr-RoRoR’R’R”RR’’RR1Ro – R’R2Ro – R”RxRo – R’ – R”RyR’ – R”

SEX-DETERMINATION.22A X22 PS-A22 PS-A XY XX22A Y22A X 22A X22 PS-A22 PS-AP A XY XX

Non Mendelian Inheritances.Non-MendelianInheritances6. Inheritansi sehubungan dengan6perbedaan jenis kelamin (sex).a. Sex-InfluencedSI fld ChCharacters.tb. Sex-LimitedLmCharacters.arar .c. Sex-Linked Characters.

6 S6a.Sex-InfluencedI fld ChCharacters.tSyn : sexSyn.:sex-sekunder.sekunder - Perobahan suara Faktor /gen ada dikedua jenis kela- Pertumbuhanminmin.rambutb t wajah.j h- Postur tubuh & Berkembang diba- dll.wah pengaruh - Pertumbuhanperbedaan kadarkelenjar mammahormonreproduksi.- Postur tubuhtubuh, dll.dll

6b. Sex-Limited6LmCharacters.arar . Baldness. FFaktor/genk /adad pddGenotype Sex &kedua jenis sex.Phenotype.yp DominanD ipdd sex BaldnessBBtertentu ( / ) dan Baldnessrecessive pd sexlainnya. BaldnessBb Contoh : Baldness.Baldness Normal bb Normal Normal

6c Sex6c.Sex-LinkedLinked Characters.CharactersHomoloogg portion between X and YorNon-homoloog portion Homoloog portion diturunkan Incopletely SexYXLinked Autosomal Inheritances. NonNon-homolooghomoloog portion SexSex-LinkedLinked. Sex-Linked X-Linked dan Y-Linked. Y-LinkedY Linked synsyn. HolandricHolandric.

X-Linked (sex-Linked)recessivei diseasesdiiin HHuman. 11. HHaemophylia,h l2. Red-greengColor-blindness,3. DMP (Dystrophia Musculorum Progressiva)4 G-6-P4.G-6-P.D.D Deficiency,Deficiency5. Adontia.

Red-greengColor-blindness P. Normal X Normal CarrierXYXXG.X - YX - XF. XXYXXXY Normal NormalXXXXY Carrier Cb.

PEDIGREE.1ST GENERATION2NDGENERATION3RDGENERATIONPropositusPp sit s CarrierC i/proband heterozygote4RDGENERATION

PROBABILITY Probabilitas turunan :priai (a)( ) : wanitait (b) 1 : 1 a b ½½ Pasangan suami-isteri dengan 5 anak :((a b))5 a5 5 a4b 10 a3b2 10 a2b3 5ab4 b5

The end.endGenetika Dasar.

HumanCytogeneticsDr. Kamajaya,MSc,SpAnd.Dept.Biologi FKFK-USUM e d a n .

HUMANCHROMOSOMES 46 ChromosomesChsomatic ( 2n2 ) 22 ppair of Autosomes XX Sex-chrom.Æ XY Sex-chrom.Sex-chrom Æ 23 Chromosomes gametic ( n ). 22 Autosomes X / Y Sex-chrom.

SEX-CHROMATIN.A. Barr-body.

Sex-chromatin.B. Drum-stick.

FLUORESCENT-BODY.

LYON-HYPOTHESIS.1. Bila dlm sbh sel terdpt 2/lbh krom-X, Krom-XKrom X yg lebih piknotik.piknotik2. Krom. Piknotik inaktif secara genetik.3. Krom. Inaktif mencegah dosis berganda.4. JJumlahmSex-chromatinm P (j(jlh-X)) -1.5. Krom-X yg piknotik random.6 Pd anak sel6.sel, krom-Xkrom X piknotik klon.klon

The chromosome. Tipe-tipe krom.p-armCentromereq-arm1231. Metacentric chromosome.2. Submetacentric chromosome.3. Acrocentric chromosome.

Chromosome-analysis. A. Cell-samples.lll1. Lymphocytes.y py2. Bone-marrow cells.3 Fibroblast3.Fibroblast.4. Amniotic fibroblast.5. Throphoblast.

Chromosome analysisChromosome-analysis.B. Lymphocytey py culture.1. Sampel : darah perifer.2 Media : HAM F2.F-10,10 TCTC-199,199 dlldll.3. Stimulasi Mitosis : PHA, Concovalin-A.4. Anti-kontaminasi bakteri dan jamur.5. Kultur di inkubator suhu 37oC,, 96% CO2& 5% O2.6 Lama kultur 67 jam6.jam.

Chromosome analysis.yC. Harvest, preparation & staining.1 Harvest : - Washing Buffer,1.Buffer- Bulging KCl 1%,- FixationFixation.2. Preparation.3. Stainingg : a. Normal Giemsa,b. Banding staining :- Trypsin-Giemsa banding.- Fluorescent-banding.Flt b di

Human Karyotype.y yp

Human Karyogram.

Human Banding Chromosome.

Chromosome banding. Band berbeda jlh dan lokasi nyay utk setiapp kromosom. Band terbentuk dariRepetitive-DNA (A-T,A-T,A-TAT dst).dst) Band penting dlm pairing kromosom pd profase. Band digunakan utk mengenalipasang an kromosom dan utkmenjadi map kromosom.

Abnormal number of human chromosomes.Chromosome non-dysjunction.A Sex chromosome non-dysjunctionA.non dysjunction.B. Autosome non-dysjunction22 ps A XYP.22 A X22 ps A1. Klinefelter syndrome XX22 A Y22 A XX2 Triplo2.Triplo-XX female syndrome22 A3. No-name ; † -4. Turner syndrome.y22 ps A XXY1.22 ps A XXX2.22 ps A -Y3.22 ps A X-4.

1 Klinefelter syndrome1. 1. Jenis kelamin pria.2. Tinggi badan disproporsional.3. Retardasi mental / - .4. Dapat menikah.5. Hypogonad-hypergonadotropin.Hypogonad hypergonadotropin.6. Gynecomasty.7. Sex-chromatinSex chromatin : ( ) satu atau lebih.8. Chromosome : 47;XXY; 48;XXYY;49;XXYYY

2 Triplo-X female syndrome.2.syndrome 1. Jenis1J i kelamink l i wanita.it2. Inteligensi variatif.3. Umumnya menikah.4. Haid sangat tidak teratur.5. Fertilitas subnormal.6. Sex-chromatin 2 atau lebih.7. Chromosom : 47;XXX, 48;XXXX atau49;XXXXX

4. Turnerurn r syndromeyn r m 1. Jenis kelamin dapat wanita atau pria.T bTerbanyakk wanita.it 2. Tubuh pendek, khas dg webbing-neck. 3. Insuffisiency mental. 4. Disgenesis gonad. 5. Primary amenorrhoe 6. Male Turner syndrome Noonan syndrome. 7. Sex-chromatin : negatif . 8. Karyotip : 45;XO, 46;XX/XY;45;XO.

Turnersyndrome

B. Autosomal non-disjunction 1.2.33.4.5.Trisomy 21 syndrome.Trisomy-21Trisomy-18 syndrome.TTrisomy-13i13 syndrome.dTrisomy-8.dll.

Trisomy-21. Synonim : Down-syndrome, Mongoloid-idiocy,Mongolism. Frekwensi : 1 dlm 600-800 kelahiran bayi hidup. Tanda-tanda :Tubuh pendek. Wajah : kecil, bulat dan rata.Hidungg pesek. Telingag : letak rendah, kecil danhipoplastis. Mata: epicanthic-fold, Brushfield spot.Tangan dan jari : pendek, simian crease,hihipoplasial i tltlg kkelingking.li kiOtOtot-otott t t hihipotonikt ik dlldll.

Trisomy-21. Retardasi mental : IQ 25-50 (imbecil).rendah, sering disertai CHD Berat-badan lahir rendah(40%), atresia duodenum,annular pancreas,Hirschprungpg disease,, anus imperforata,p,tracheoesophageal fistula, leukemi limfoblastikakut, dll. Sitogenetika : 1. Klasik : 47;XX/XY;21 .2. Translokasi : 46,XX/XY; D/G trans. /G/G trans 5%3. Mosaik : 46;XX/XY-47;XX/XY;21 1 %.

TrisomyTrisomy-21.

2.2. Trisomy-18. Tanda-tandaT d t d : Kepala panjang, wajah : kecil, bulat,micronathiamicronathia,telinga letak rendah, cutis laxa, horse-shoekidney,syndactyly, hipertelorisme,, ptosis, dll. Retardasi mental yang hebat, SitogenetikaSitogenetika : Trisomi kromosom no.18.no 18

Sindrom trisomy-18.

2.3. TrisomiTrisomi-13.13.Tanda-tanda : Microcephaly,Labiopalatoschizis,Microcephaly Labiopalatoschizis abnormalstruktur CNS (arrhinencephaly),anophthalmia/ micropthalmia, coloboma-iris,CHD cystic kidneyCHD,kidney, Meckel diverticulum,diverticulumcryptorchismus, uterus bicornis, dll. BB-lahir rendah,, seringg apnoepdan cyanosis,y,Frank-seizure (myoclonic attack) danumumnya penderita meninggal hari-I atausebulan. Sitogenetika : Trisomi kromosom no.13. Dapatpula bentuk translokasi, atau mosaik.

Sindrom trisomy-13.

2.4. Trisomy-8.Tanda-tandaTd t d : Sulit didiagnose sebab tanda-tandanyavariatif,, Tubuh pendek, kepala relatif besar, bersudutdan cenderung bagian depan menonjol, telingalebar dan malformasi,malformasi micronathia,micronathia ptosis,ptosisstrabismus, cryptorchismus, hypospadia,hydronephrosis, atrio-ventricular septal defect, IQ rendah,d h kkurang ddarii 3030, speechh problem,bldll. SitogenetikSitogenetik : sering dlm bentuk mosaik.

Trisomy-8.

EFICIENTbabaTranslocation homoloog(duplication)

The effects ofchromosome aberration. 1. Fragil chromosome.2. Deficientfchromosome.3. Inversion chromosome.4 Translocation :4.a. Homoloogb Heteroloogb.Heteroloog.

Deletionlsyndrome. ( 4p- ) syndrome. ( 55p- ) syndromed Cri-du-ChatC i d Ch tsyndrome (13q- ) syndrome.

1. ( 4p-) syndrome. Mental retardasi, hypotonic. BB-lahir rendah, bone-age, TB, BB dan pertumbuhan motoriskurang berkembang. HHypertelorisme,p t l ism matam t antintimongoloid, epicantic fold, ptosis,strabismus.strabismus Hypospadia, cryptorchismus. CHD, dll.

( 4p- ) syndrome.