8 chromosome disorder
TRANSCRIPT
Chromosome disorders
Weiying Jiang Department of Medical Genetics
P33
Human chromosome
What is chromosome?
Chromosomes are complex structures located in the cell nucleus, they are composed of DNA, histone and non-histone proteins, RNA , and polysaccharides. They are basically the "packages" that contain the DNA.
A group——1 ~ 3
B group——4 ~ 5
C group——6 ~ 12 +X
D group——13 ~ 15
E group——16 ~ 18
F group——19 ~ 20
G group——21 ~ 22 +Y
Classification
Metacentric(Chromosome 1)
Submetacentric(Chromosome 9)
Acrocentric(Chromosome 14)
Methods of chromosome analysis
Karyotype analysis
Methods of chromosome analysis
Karyotype analysis
(G banding )
Methods of chromosome analysis
Fluoresent in-situ hybridization (FISH)Utilizing fluorescently labeled DNA probes to detect or confirm gene or chromosome abnormalities that are generally beyond the resolution of routine Cytogenetics
Metaphase FISH
Interphase FISH
FISH can be used in interphase cells to determine the chromosome number of one or more chromosomes as well as to detect some specific chromosome rearrangements that are characteristic for certain cancers. The primary advantage of interphase FISH is that it can be performed very rapidly if necessary, usually within 24 hours, because cell growth is not required.
Comparative Genomic Hybridization
( CGH)ATCGGATCATGCGTA
TAGCCTAGTACGCAT
Disadvantages:
Resolution
Technical difficulties
10 mega-bases for losses
2 mega-bases for gains
Providing the start point for position cloning, but the precise localization
Array CGH
Advantages:
Resolution
30,000 overlapping mapped
clones (one clone per mega-base)
Oligonucleotide array includes up 500,000 probes
Chromosome abnormality
Numerical abnormality
Structural abnormality
Aneuploidy
Polyploidy
translocation
deletion
insertion
inversion
rings
isochromosome
Numerical abnormality
46 chromosomes
23 chromosomes = one set of chromosomes
Diploidy
Aneuploidy:
One or a few
chromosomes ,except 23 ones ,
above or below the normal
chromosome number. For
example, three number 21
chromosomes or trisomy 21.
The common aneuploidy:
Patau syndrome: (trisomy 13)
Edwards syndrome: (trisomy 18)
Down’s syndrome: (trisomy 21)
The common aneuploidy:
Turner’s syndrome:
(45, X)
XX
X X
l l l l
Normal
Non-disjunction
In meiosis
Mosaicism
Non-disjunction
During Mitosis
Polyploidy
More than two sets of chromosomes per nucleus.
23 chromosomes = one set of chromosomes
69,XXY 92,XXXY
Diandry Digyny
Structure of chromosome abnormality
46,XY,t(5;8)(q31.1;p23).
A
CB
D
Synapsis
Robertsonian Translocation
46,XX,del(16)(q13q22
46,XY,inv(10)(q11.23q26.3).
Inversion
A
CB
D
Synapsis
Pericentric inversion
Paracentric inversion
1
2
34
1
42
31
2
43
46,XY,+13,dic(13;14)(p11.2;p11.2).
Ring chromosome
Chromosome abnormality
Numerical abnormality
Structural abnormality
Aneuploidy
Polyploidy
translocation
deletion
insertion
inversion
rings
isochromosome