复旦大学：《医学遗传学 Medical Genetics》课程教学资源（PPT课件讲稿）Chromosome disorders

Medical genetics Chromosome disorders Lecturer: David Saffen Ph D Laboratory for Molecular Neuropsychiatric Genetics Department of Cellular and Genetic Medicine School of Medicine, Fudan University saffen@fudan.edu.cn

Medical Genetics: Chromosome disorders Lecturer: David Saffen. Ph.D. Laboratory for Molecular Neuropsychiatric Genetics Department of Cellular and Genetic Medicine School of Medicine, Fudan University saffen@fudan.edu.cn

Next three lectures Chromosome disorders(Nov. 22) 2. Single gene( Mendelian")disorders(Nov 29) 3. Polygene(complex) disorders(Dec 6 医学遗传学 Textbook of Medical Genetics:医学遗传学 ( Thompson& Thompson医学遗传学)第7版中英改编版 北京大学医学出版社lsBN:978-781116785-6( chapters5-8)

Next three lectures: 1. Chromosome disorders (Nov. 22) 2. Single gene (“Mendelian”) disorders (Nov. 29) 3. Polygene (“complex”) disorders (Dec. 6) Textbook of Medical Genetics: 医学遗传学 (Thompson & Thompson医学遗传学) 第7版中英改编版 北京大学医学出版社ISBN:978-7-81116-785-6 (Chapters 5-8)

Chromosome disorders After listening to this lecture you should have a better understanding of 1. The role karyotype analysis in the discovery and diagnosis of human chromosome disorders 2. The molecular and cellular origins of chromosome abnormalities 3. Several famous chromosome disorders 4. The role of dNa methylation in the regulation of gene expression and human disease

Chromosome disorders After listening to this lecture you should have a better understanding of: 1. The role “karyotype” analysis in the discovery and diagnosis of human chromosome disorders 2. The molecular and cellular origins of chromosome abnormalities 3. Several famous chromosome disorders 4. The role of DNA methylation in the regulation of gene expression and human disease

Outline A. The human genome and its chromosomes B The origin of chromosome abnormalities C Chromosome disorders

Outline: A.The human genome and its chromosomes B. The origin of chromosome abnormalities C. Chromosome disorders

A. The human genome and its chromosomes The human genome Structures of human chromosomes The human karyotype Staining metaphase chromosomes

A. The human genome and its chromosomes • The human genome • Structures of human chromosomes • The human karyotype • Staining metaphase chromosomes

The human genome(in numbers) Haploid cells(gametes) contain -3 1 X 109 and diploid(somatic cells: -62x 10 bp DNA Laid end-to-end the chromosomal dna in each diploid cell would extend 2 meters The total length of chromosomal DNA in the human body (~50X1012cels-100X109km Distance from Sun to Neptune 4.55X109km Neptunes orbit around the sun 28.6X109km

The human genome (in numbers) • Haploid cells (gametes) contain ~ 3.1 x 109 and diploid (somatic) cells: ~ 6.2 x 109 bp DNA • Laid end-to-end, the chromosomal DNA in each diploid cell would extend ~ 2 meters • The total length of chromosomal DNA in the human body (~50 x 1012 cells) ~ 100 x 109 km Distance from Sun to Neptune: ~ 4.55 x 109 km Neptune’s orbit around the sun ~ 28.6 x 109 km

Composition of the human genome 1.1%~4% <2% ~44% 32% ~45% ~65% mitochondrial genome 16.6kb nuclear genome highly conserved sequences poorly conserved sequences protein-coding genes transposon-based repeats RNA genes, regulatory sequences heterochromatin other sequences

Composition of the human genome 16.6 kb

Composition of transposon-based repeats 45%of the human genome LINEs LINE-1 family ~600,000 autonomous nonautonomous LINE-2 family 370,000 ORF1 ORF2(poD LINE-3 family 44,000→P SINES 6-8 kb Alu family ~1,200,000 MIR ~450,000 100-400bp ∥|R3 85,000 retrovirus-like(LTR transposons) LTR HERV families ~240,000 P gag pol (env) LTR (gag) LTR MaLR 285,000 6-11kb 1.5-3kb DNA transposon fossils MER1(Charlie) ~213,000 transposase MER2 (Tigger 68000 2-3kb others 60,000 80 bp-3 kb ORF open reading frame, gag= viral capsid protein; pol= reverse transcriptase, env=envelope protein, LTR= long terminal repeat

Composition of transposon-based repeats (~45% of the human genome) ORF = open reading frame, gag = viral capsid protein; pol = reverse transcriptase, env = envelope protein, LTR= long terminal repeat

Composition of major classes of high-copy number tandemly repeated DNA (6.5% of human genome Chromosomal Class Array size Repeat unit location Satellite dna hundreds of kb alphoid DNA 171bp centromeric β(Sa3 A family) 68b heterochromatin Satellite 1 25-48bp Satelitte 2 ATTCC/GGAAT Satellite 3 ATTCC/GGAAT Minisatellite dNA 0.1-20kb Telomeric TTAGGG telomeres Hypervariable 9-64bp euchromatin Microsatellite DNA <100 bp often 1-4 bp widely dispersed Diverged forms of this sequence; **primarily"constitutive heterochromatin as opposed to faculatitive heterochromatin

Composition of major classes of high-copy number tandemly repeated DNA (6.5% of human genome) Class Array size Repeat unit Chromosomal location Satellite DNA a(alphoid DNA) b(Sau3A family) Satellite 1 Satelitte 2 Satellite 3 hundreds of kb 171 bp 68 bp 25-48 bp ATTCC/GGAAT* ATTCC/GGAAT centomeric heterochromatin** “ “ “ Minisatellite DNA Telomeric Hypervariable 0.1-20 kb TTAGGG 9-64 bp telomeres euchromatin Microsatellite DNA <100 bp often 1-4 bp widely dispersed *Diverged forms of this sequence; **primarily “constitutive” heterochromatin as opposed to “faculatitive” heterochromatin

Structures of human chromosomes Metaphase y and x chromosomes (scanning electron micrograph)

Structures of human chromosomes Metaphase Y and X chromosomes (scanning electron micrograph)