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