CHROMOSOMAL ABNORMALITIES

PRESENTED BY:DR. BISWAJEETA SAHA(PGT,1ST YR),MODERATOR-DR.A.K.ADHYA(ASST. PROF),DEPT OF PATHOLOGY,KIMS,BBSR

NORMAL KARYOTYPE Karyotype: a picture of the chromosomes from a single cell.

International system for

human cytogenetic

nomenclature.

eg- Xp21.2

Eg-47,XY,+21

NUMERICAL ABNORMALITIES

Euploid-any exact multiple of haploid

Aneuploidy-chromosome compliment that is not an exact

mutiple of 23

Nondisjunction

Anaphase lag

Mosaicism-mitotic error in early development give rise to 2

/more population of cells with different chromosomal

complement in some individual EG-45X/47XXX mosaic

Deletions-loss of a portion of chromosome

STRUCTURAL ABNORMALITIES

Eg-46,XY,del(16)(p11.2p13.1)

RING CHROMOSOME

Eg-46,XY,r(16)

Insertion

Inversion-2 breaks,turns upside down and re-attaches

Eg-inv(9)(p11q12)

Isochromosome-one arm is lost,other arm is reduplicated

Translocation-one segment transferred to another.

Eg-46,XY,t(2:5)(p12;q14)

CLINICAL ABNORMALITIES

SPONTANEOUS ABORTIONS

1 in 200 live born children is chromosomally abnormal

95% of chromosomally abnormal conceptus are aborted

spontaneously

Abortion mostly occurs in 1st trimester

DOWN SYNDROME

Incidence-1 in 700

95% have trisomy 21,chromosome no 47

1% cases are mosaics.-mitotic nondisjunction

4% cases-extra chromosomal material derives from presence of

robertsonian translocationof long arm of chromosome 21 to

acrocentric chromosome.

10 to 20 fold increased risk of deveoping leukemia

CHROMOSOME 22q11.2 DELETION SYNDROME

Small deletion of band q11.2 on long arm of chromosome 22. 1 in 4000 births Congenital heart defects ,palatal abnormalities, facial

dysmorphism, developmental delay,T-cell immunodeficiency and hypocalcemia

High risk for schizophrenia and bipolar disorder

TRISOMY 18

Incidence 1/8000

Overlaps with trisomy 13

Sever Mental retardation

>90% dead in 1st year

Small face with prominant occiput

Small sternum and pelvis

Flexion deformity of the finger

VSD and horseshoe kidney

TRISOMY 13(PATAU SYNDROME)

Severe developmetal retardation

Incidence 1/20000

90% dead in the 1st year

Midline brain defect

Malformed ear

Micropthalmos and coloboma

Scalp defect

CYTOGENETIC DISORDERS AFFECTING SEX CHROMOSOME

More common than autosomal aberrations.

Lyon hypothesis

TURNER SYNDROME Complete or partial monosomy of X chromosome Hypogonadism in phenotypic females 1 in 2000 live born females 57% missing an entire X chromosome-45,X karyotype 14% have structural abnormalities of X chromosome 29% are mosaics Structural abnormalities are- Deletion of small arm-isochromosome of long arm-46,X,i(X)(q10) Deletion of portion of both long and short arms-ring chromosome-46,X,r,(X) Deletion of portion of short or long arm-46X,del(Xq) Mosaic patterns- 45,X/46,XX 45,X/46,XY 45,X/47XXX 45,X/46,X,i(X),(q10)

Female, short stature, primary amenorrhea, sterility, spares

hair and underdeveloped breast

Neonatal: wide spaced nipple, lymphedema , shield chest,

KLINEFELTER SYNDROME

Male hypogonadism occur when there are 2 /more X

chromosome and one /more Y chromosome.

1 in 660 live male births

Eunuchoid body habitus,abnormally long legs,small atrpohic

testis,lack of secondary male characteristics

Increased incidence of type 2 diabetes,metabolic syndrome

Higher risk of breast cancer,extragonadal germ cell tumor and

autoimmune diseases

47,XXY-90% cases

15% cases are mosaics

HERMAPHRODITISM GENETIC SEX

PHENOTYPIC SEX

PSEUDOHERMAPHRODITISM

TRUE HERMAPHRODITISM

FEMALE PSEUDOHERMAPHRODITISM-excessive and

innapropriate exposure to androgenic steroids during early

gestation

MALE PSEUDOHERMAPHRODITISM-extremely

heterogenous.most common –defective virilization of male

embryo(complete androgen insensitivity syndrome)

KARYOTYPING

3 main methods to identify chromosomes

G BANDING-------giemsa

Q BANDING-------quinacrine

R BANDING-------reverse

SUBCLASSIFICATIONS OF BANDING METHODS ISCN 1985

3 letter code to describe banding techniques.

Ist letter---type of banding

2nd letter—general technique

3rd letter—the stain

Eg-QFQ------Q band by flourescence using quinacrine

G BANDING

System of dark and light bands throughout the euchromatin

part of chromosome

Staining technique where chromosomes are treated with

trypsin then with giemsa stain

Needs metaphase

Culture cells until sufficient mitotic activity

Add colchicine to arrest in metaphase

TERMS AND DEFINITIONS OF VARIOUS ABERRATIONS OF CHROMOSOMES

Ring( r)

Dicentric(d) Hyperdiploid (h)

Chromosome gap (sg) Chromatid

deletion (td)

Fragment (f) Acentric fragment

(af)

Translocation (t) Triradial (tr)

Quadriradial (qr)

Complex rearrangement (cr)

Polyploid (pp) or endoreduplication

FLOURESCENT IN SITU HYBRIDISATION(FISH)

Fluorescence in situ hybridization (FISH) uses fluorescent

molecules to “paint” genes or chromosomes.

This technique is for gene mapping, identification of

chromosomal abnormalities

FISH involves the use of short sequences of single-stranded

DNA (probes) which are labeled with fluorescent tags, to

hybridize, or bind, to the complementary DNA to see the

location of those sequences of DNA under the fluorescent

microscope.

metaphase FISH interphase FISH

ADVANTAGES OF FISH

Rapid

High efficiency of hybridization and detection

Lots of cells can be analyzed

Cells do not have to be replicating

SPECTRAL KARYOTYPING

Chromosomal and subchromosomal painting probes that make use of sorted or microdissected chromosomes

Mixtures of fluorophores used to separately label chromosome-

specific probes

These are mixed and hybridized en masse

Interpreted via spectral interferometer

Tremendously useful in detecting insertions and translocations,

especially in cancers.

THANK

YOU