CHROMOSOMAL ABNORMALITIES

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
 STRUCTURAL ABNORMALITIES
 Deletions-loss of a portion of chromosome

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.
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