LECTURE – 3 Learning objectives

2. LECTURE – 3Learning objectives Cytogenetics Chromosome Chromosomal disorders (autosomal)

3. CYTOGENETICS Karyotyping • by detecting errors in chromosome # / structure • by study under microscope, photography & image analysis Study of chromosomes by morphological analysis

4. CYTOGENETICSMETHODOLOGY • Bone marrow, cancers, testis ; lymphocytes with addition PHA • Staining method : G/Q/R bands • Special methods : C, G, G-II, NOR, DAPI, T staining , SKY • Special culture - BRDU, sister chromatid exchange (SCE)

5. Karyotyping Harvesting procedure

7. CHROMOSOME STRUCTURE • Chromatids • Centromere • p /q arms • Telomere • Satellites TTAGGG

8. Xp2.13

9. CHROMOSOMAL DISORDERS • Late maternal age • Irradiation • Drugs / chemicals • Viruses Etiology After35

10. MECHANISMS ALTERING CHROMOSOME # • Non – disjunction • Anaphase lag • Multiple gametic fertilization

11. Cytogenetic nomenclature • Aneuploidy : variation # (2n + 1 / –1) • Hyperploidy - > 46 chromosomes • Hypoploidy - < 46 chromosomes • Trisomy / monosomy : 3/one in a pair • Haploid - 1 single set (23) : chromo - • Euploid:x haploid: diploid, tetraploid • Mosaicism: presence of more than 1 cytogenetically distinct cell lines

12. Mosaicism

14. STRUCTURAL CHROMOSOMAL ABERRATIONS

15. CYTOGENETIC NOMENCLATURE • Normal: 46, XX / 46, XY • Monosomy: 45, X • Trisomy: 47, XX, +21 / 47, XXY • Deletion : 46, XY, del(5) (p13) • Inversion: 46, XY, inv(5) (p13-15) • Ring chromosome: 46, XY, r(14) • Isochromosome: 46, XY, i(Xq) • Translocation: 46, XX, t(2:5)(q31; p14) • Mosaicism: 46, XX / 47, XX, +21

17. CYTOGENETIC DISORDERS • Non - disjunction / anaphase lag : • gametogenesis – trisomy / monosomy • in early development in mosaicism • Monosomy : autosome incompatible with life, some trisomies may be • Monosomy / trisomy of sex chromosomes more compatible • Autosomal mosaicism less common • Structural aberration :chromosomes

18. CYTOGENETIC DISORDERS • Cytogenetic disorders involving autosomes: Down syndrome, Edward syndrome, Patau synd. • Cytogenetic disorders involving sexchromosomes : Klinefelter syndrome, XYY syndrome, Turner syndrome, XXX/XXXX syndromes

19. DOWN SYNDROME

20. DOWN SYNDROME TRISOMY 21 • Most common genetic cause of mental retardation in children • Incidence : 1 / 800 live births • Maternal age : 1 in 1550 below 20 year, 1 in 25 over 45 years • Parents : of normal karyotype • Most meiotic non – disjunction • 95% extra CH of maternal origin

21. DOWN SYNDROME • Karyotype – trisomy 95% : 47, XX, +21 • Translocation 4%: 46, XX, +t (14q 21q) • Mosaic type 1% : 46, XX / 47, XX,+21

22. CLINICAL FEATURES • Facial profile: flat, oblique palpebral fissures, epicanthic folds • Severe mental retardation • Congenital heart dis., septal defects • High risk of acute leukemia • Serious infections are common • Premature Alzheimer's dis. after 39 • Average life expectancy of 30 yrs

24. CRI du CHAT SYNDROME • Karyotype : – 5p • Clinical features : • Mewing cat like cry • Severe mental retardation • Congenital heart disease • Survival: some into adult life

26. SnapShot Mother nature stumbling !

27. . Beautiful young people are accidents of nature. Graceful old people are the work of art.

28. Thank You