HUMAN CHROMOSOME KARYOTYPING M Mansyur Romi CHROMOSOME The

HUMAN CHROMOSOME & KARYOTYPING M. Mansyur Romi

CHROMOSOME • The highest order of DNA coiling • Each species has a characteristic number and size of chromosomes, known as karyotype. • The normal number of Xsomes in a nucleus: diploid (2 n) • During gametogenesos 2 n is halved one of eachpair = haploid (n)

Coiling of chromosomal/ nuclear DNA

CHROMOSOME – Duplicate themselves before the onset of cell division – Appear during metaphase – After replication each Xsome consist of two identical copies: sister chromatids juncside by side but still connected at the centromer.

CHROMOSOME – Structure: • Centromer (primary constriction) • Long arm (p) • Short arm (q) – Banding patterns: – Heterochromatin: highly condensed – Contains four known genes, its function is not well understood – Flanked to centomers – Euchromatin: more lightly – Contains most of the genes

Human kariotype 46, XY

Human Genome 23 chromosomes – 60, 000 – 70, 000 genes – 3 x 109 b. p. – 3, 000 c Morgans 1 Chromosome : – 2, 000 – 5, 000 genes – 1, 3 x 108 b. p. – 130 c. M

1 Chromosomal microband • 50 – 100 genes • 3 x 106 • 3 c. M 1/10 Chromosomal microband • ~230 x the length of one globin gene • 1/6 x the length of the duchenne locus

TURNER SYNDROME • Karyotipe 45, X • Diidentifikasi pertama kali tahun 1928 oleh Dr. Henry H Turner • Insiden 1/4000 bayi lahir hidup perempuan • Etiologi : Tidak adanya kromosom seks paternal (70%) • Biasanya lethal dalam uterus namun kompatibel dan dapat bertahan setelah kelahiran (99% abortus spontan)

Karyotype Turner Macam karyotipe 45, X 50% 46, X, i(Xq) 15% 45, X / 46, XX mosaik 15% 45, X / 46, X, i(Xq) mosaik ~5% 45, X, abnormalitas lain ~5%

Gambaran Klinis Turner • Perawakan pendek (rata 2 55 inci~137 cm) • Kelainan Kardiovaskular, penyebab tertinggi kematian • IQ normal atau diatas rata • Terdapat disgenesis gonada (ovarian dysgenesis)

KLINEFELTER SYNDROME • Karyotipe 47, XXY • Variant : 48, XXYY ; 48, XXXY ; 49, XXXXY • Etiologi : error pada : • Paternal Meiosis I • Maternal Meiosis I ~ usia ibu • Maternal Meiosis II • Post zigotic Mitotic ~ Mosaicism • Karena kegagalan rekombinasi Xp / Yp pada pseudoautosomal region • Insiden : 1/1000 bayi laki-laki lahir hidup • Merupakan kelainan kromosom seks pada manusia yang pertama kali dilaporkan

Karyotype Klinefelter

Kelainan 2 pada Klinefelter Syndrome • IQ rata-rata 85 – 90 • Anggota gerak yang panjang dan kurus • Pubertas usia normal namun testis kecil (< 2, 5 cm) • Hampir selalu infertil karena kegagalan perkembangan Germ Cell • Kadang-kadang didapatkan ginekomasti • Penurunan produksi testosteron • Juga didapatkan kesulitan belajar, membaca, bahasa, poor social adjustment

Karyotipe 47, XYY

XYY Syndrome • IQ rata-rata 10 -15 point dibawah rata 2 • Hiperaktif • Agresif atau sifat psikopatologi bukan gambaran umumnya • Gigi yang besar 2, dahi menonjol, telinga panjang, jari relatif panjang • Fertilitas normal, pubertas biasanya terlambat sampai 6 bulan

Genetic material

Gene Mapping § Assignment of a locus to a specific chromosome and / or § Determining the sequence of genes and their relative distance from one another on a specific chromosome Two types of map: ü physical map ügenetic or linkage map

GENE STRUCTURE • Promoter: the sequence elements located 5’ to the gene, which fix the site of initiation of transcription and control m. RNA quantity and sometimes tissue specificity • Exon: the transcribed regions of the gene that are present in mature m. RNA and usually contain coding information.

GENE STRUCTURE • Intron: a segment of a gene that is initially transcribed into RNA but is then removed from the primary transcript by splicing together the exon sequences on either side of it. • Enhancers: DNA sequences that act in CIS to increase transcription of a nearby gene. These can act in either orientation 5’ or 3’ to the gene and may act at considerable distance from the gene.

CHROMOSOME Xsomes of eukaryotes consist of: • DNA • Histone proteins both are constant and form nucleosome • Nonhistone proteins • RNA both vary with the metabolic activity of the cells