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

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

CYTOGENETICS METHODOLOGY 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)

Karyotyping Harvesting procedure

CHROMOSOME STRUCTURE TTAGGG Chromatids Centromere p / q arms Telomere Satellites TTAGGG

Xp2.13

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

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

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

Mosaicism

STRUCTURAL CHROMOSOMAL ABERRATIONS

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

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

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

DOWN SYNDROME

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

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

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

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

Mother nature stumbling ! SnapShot Mother nature stumbling !

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

Thank You