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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 109 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 106
• 3 cM
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 (rata2 55 inci~137 cm)
• Kelainan Kardiovaskular, penyebab
tertinggi
kematian
• IQ normal atau diatas ratarata
• 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
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 10-15 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
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:
 physical map
genetic or linkage map
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