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Морфологија и градбана хромозоми
Цитогенетика
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Od DNK do
metafaznog
hromozoma
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Hromozomi posmatra
elektronskim mikrosk
hromatida
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Центромерен регион
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MORFOLOŠKI TIPOVI HROMOZOMA
A – telocentričan
B – akrocentričan
C – submetacentričan
D – metacentričan (p = q)
p kra
q kra
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• Chromosomes are arrang
by:
1. size
2. location of centromere
• Banding patterns also hel
identify chromosomes
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Kariotip
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Kariogram
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Полов диморфизам
• Машки
- хетерогаметни
• Женски
- хомогаметни
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Полови хромозоми
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Барово телце
• секс- хроматин
• Barr и Bertram во 1949год
• еден микрон
• хетерохроматичен хромозом
• 12-18
• Lyon-ова хипотеза
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Барово телце
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Mary Lyon
Barova tela
(pokazana strelicam
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Idiogram
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Hromozomi 4 i
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2n = 46
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A B
C
D
F
E
G
2n = 46
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A A A A
HOMOZIGOT (AA)
A A a a
HETEROZIGOT (Aa
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a a a a
HOMOZIGOT (aa )
a a
X
HEMIZIGOT (XaY)
Y
XX
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• The human genome is stored on 23 chromosome pairs and in the
small mitochondrial DNA.
• Twenty-two of the 23 chromosomes belong to autosomal chromo
pairs, while the remaining pair is sex determinative. The haploid h
genome occupies a total of just over three billion DNA base pairs.• The Human Genome Project (HGP) produced a reference seque
the euchromatic human genome, which is used worldwide in
the biomedical sciences.
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• The haploid human genome contains about 23,000 protein-
coding genes, which are far fewer than had been expected b
sequencing.
• In fact, only about 1.5% of the genome codes for proteins, w
the rest consists of non-coding RNA genes regulatorysequences, introns and non-coding DNA.
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Полови хромозоми
• X-хромозом
-субметацентичен
- C-група
• Y-хромозом
-акроцентичен
-G-група
-полиморфизам
-холандричен сектор
-генот за машка сексуал
диференцијација (SR-генот за сперматогенез
(H-Y) антигенот
-генот кој го инхибира развитокот на Милерканали
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• There are estimated to be between 20,000 and 25,000 huma
protein-coding genes.
• The estimate of the number of human genes has been repe
revised down as genome sequence quality and gene
finding methods have improved. In the late 1960s, predictionestimated that human cells had as many as 2,000,000 gene
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Human genes are
distributed unevenly
across the
chromosomes. Each
chromosome
contains various
gene-rich and gene-
poor regions, which
seem to be correlated
with chromosome
bands and GC-content.
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• Most aspects of human biology involve both genetic (inherite
non-genetic (environmental) factors.
• Some inherited variation influences aspects of our biology th
not medical in nature (height, eye color, ability to taste or sm
certain compounds, etc.).
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• some genetic disorders only cause disease in combination
appropriate environmental factors (such as diet).
• With these caveats, genetic disorders may be described as
clinically defined diseases caused by genomic DNA sequenc
variation. In the most straightforward cases, the disorder canassociated with variation in a single gene.
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• For example, cystic fibrosis is caused by mutations in the C
gene, and is the most common recessive disorder in caucas
populations with over 1,300 different mutations known.
• Disease-causing mutations in specific genes are usually sev
terms of gene function, and are fortunately rare, thus geneticdisorders are similarly individually rare.
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GENE DISEASE DOWN SYNDROME
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The human karyotype
• There are 44 autosomes and 2 sex chromosomes in the
human genome, for a total of 46. Karyotypes are pictures
of homologous chromosomes lined up together during Meta
of meiosis. The chromosome micrographs are then arranged
size and pasted onto a sheet.
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X-linked and Y-linked inheritanc
• linked genes are found on the sex X chromosome. X-linked
just like autosomal genes have both dominant and recessive
Recessive X-linked disorders are rarely seen in females and
usually only affect males. This is because males inherit their
chromosome and all X-linked genes will be inherited from th
maternal side.
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• Y-linked inheritance occurs when a gene, trait, or disorder is
transferred through the Y chromosome. Since Y chromosom
only be found in males, Y linked traits are only passed on fro
father to son.
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Genetic code
• The genetic code is the set of rules by which information enc
in genetic material (DNA or mRNA sequences)
is translated into proteins (amino acid sequences) by living c
• The code defines how sequences of three nucleotides,
called codons, specify which amino acid will be added nextduring protein synthesis.
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• Not all genetic information is stored using the genetic code. All orga
DNA contains regulatory sequences, intergenic segments, chromoso
structural areas, and other non-coding DNA that can contribute grea
to phenotype.
• Those elements operate under sets of rules that are distinct from thto-amino acid paradigm underlying the genetic code
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Non-coding DNA
M ki K
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Making a Karyotype
Amniocentesis • Performed: no earlier tha
16th week of pregnancy
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Amniocentesis 16th week of pregnancy• Fetal Cells used to make
Karyotype to check forchromosome abnormalitie
• Biochemical analysis ofamniotic fluid can detect various biochemical disorde.g. tay sachs
• - Turn around time: fetal must be cultured for at lea10 days before they can be
karyotyped!• Risks involved? Increased
(about 1%) of spontaneouabortion.
Chorionic Villi Sampling (CVS)
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Chorionic Villi Sampling (CVS)
• Performed 8 to 10 weeks inpregnancy.
• Karyotype Using villi cells
• DNA analysis
• Biochemical tests can be doon tissue
• Turn around time:
Karyotype can be produced samday CVS is performed!
Risks?:
Spontaneous apportion (slightly higthan with amnio.)
Can lead to malformation of fingertoes (in .3% of cases)
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FISH (fluorescentna
in situ hibridizacija)
Humani hr. 4 obojen fuloresecntonom bojom
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Humani hr. 4 obojen fuloresecntonom bojom
Chromosome painting primenom FISH meto
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p g p
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Sky Karyotyping
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Sky Karyotyping
This technique allows each chromosome to be identi
individually using special hardware and software.
Sk K t i
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Sky Karyotyping
Cancer Cells