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 (2n) During gametogenesos 2n 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 side 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 10 9 b.p. –3,000 c Morgans 1 Chromosome : –2,000 – 5,000 genes –1,3 x 108 b.p. –130 cM

1 Chromosomal microband 50 – 100 genes 3x cM 1/10 Chromosomal microband ~230 x the length of one globin gene 1/6 x the length of the duchenne locus

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) TURNER SYNDROME

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 (rata2 55 inci~137 cm) Kelainan Kardiovaskular, penyebab tertinggi kematian IQ normal atau diatas ratarata Terdapat disgenesis gonada (ovarian dysgenesis)

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 KLINEFELTER SYNDROME

Karyotype Klinefelter

Kelainan2 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 point dibawah rata2 Hiperaktif Agresif atau sifat psikopatologi bukan gambaran umumnya Gigi yang besar2, dahi menonjol, telinga panjang, jarijari relatif panjang Fertilitas normal, pubertas biasanya terlambat sampai 6 bulan

Genetic material

 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: physical map genetic or linkage map Gene Mapping

GENE STRUCTURE Promoter: the sequence elements located 5’ to the gene, which fix the site of initiation of transcription and control mRNA quantity and sometimes tissue specificity Exon: the transcribed regions of the gene that are present in mature mRNA 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