浙江大学：染色体病 Chromosomal Disorders（张咸宁）

Chromosomal disorders 张成宁 zhangxianning l anju.edu.cn Tel:13105819271:88208367 Office: A705, Research Building 2012/09

Chromosomal Disorders 张咸宁 zhangxianning@zju.edu.cn Tel：13105819271; 88208367 Office: A705, Research Building 2012/09

Chromosome Disorders Are a major Category of Genetic Disease Large proportion of Reproductive wastage(miscarriages) Congenital malformations Mental retardation Significant role in pathogenesis of malignancy

Chromosome Disorders Are A Major Category of Genetic Disease • Large proportion of: – Reproductive wastage (miscarriages) – Congenital malformations – Mental retardation • Significant role in pathogenesis of malignancy

Chromosome Disorders Are a major Category of Genetic Disease Specific chromosomal abnormalities are: Responsible for >100 identifiable syndromes Collectively more common than all of the Mendelian single gene disorders together!

Chromosome Disorders Are A Major Category of Genetic Disease • Specific chromosomal abnormalities are: – Responsible for >100 identifiable syndromes – Collectively more common than all of the Mendelian single gene disorders together!

Chromosome Disorders Are a major Category of Genetic Disease 1% of live births 2 of prenatal diagnoses in women >35 yrs old 50% of all first trimester spontaneous abortions

Chromosome Disorders Are A Major Category of Genetic Disease – ~ 1% of live births – ~ 2% of prenatal diagnoses in women >35 yrs old – 50% of all first trimester spontaneous abortions

What are the indications for ordering a chromosome analysis? Growth and · Pregnancy with developmental advanced maternal abnormalities age”(AMA) Family history of · Stillbirth/ neonatal chromosome death abnormalities Infertility/history of Infertility pregnancy loss N aplasia

What are the indications for ordering a chromosome analysis? • Growth and developmental abnormalities • Family history of chromosome abnormalities • Infertility • Pregnancy with “advanced maternal age” (AMA) • Stillbirth/neonatal death • Infertility/history of pregnancy loss • Neoplasia

How is a karyotype(核型 pl repared? Sample: blood, skin, amnio, cvs Cells grown in culture Blocked in metaphase using colchicine Spread on slide and stained Abnormalities detected by number, morphology and banding pattern

How is a karyotype（核型） prepared? • Sample: blood, skin, amnio, CVS • Cells grown in culture • Blocked in metaphase using colchicine • Spread on slide and stained • Abnormalities detected by number, morphology and banding pattern

XX XX XX XX XX XX XXXX XX XX XX 8I I XX Karyotype Analyse metaphase spread 5 ml venous blood igest with trypsin and st Add phytohemagglutin ith Giemsa and culture medium Culture at 37C Spread cells onto for 3 days slide by dropping Add colchicine and hypotonic saline Cells fixed

Centromere pracroemosome Anatom p(short arm) q (long arm) 3456 Size Banding pattern( giemsa stain) :昌翡異甾 Heterochromatin异染色质 789101112 (inactive, condensed)-dark Euchromatin常染色质 131415161718 (active, decondensed)-light 州s镇“ 19202122XY

Chromosome Anatomy • Centromere placement • p (short arm) • q (long arm) • Size • Banding pattern (Giemsa stain) – Heterochromatin 异染色质 (inactive, condensed) - dark – Euchromatin 常染色质 (active, decondensed) - light

Interphase metaphase nuclei Giemsa staining(G-banding)

Interphase & Metaphase Nuclei Giemsa Staining (G-banding)

Normal human male Karyotype Individual Chromosomes Cut from Metaphase Spread Hk义 )K#)台7 -】}

Normal Human Male Karyotype Individual Chromosomes Cut from Metaphase Spread