This document discusses chromosomal abnormalities, including both numerical and structural abnormalities. It provides examples of various chromosomal abnormalities such as trisomy 21 (Down syndrome), trisomy 18, trisomy 13 (Patau syndrome), Turner syndrome, and Klinefelter syndrome. It also discusses methods used in cytogenetic analysis such as karyotyping, G-banding, fluorescent in situ hybridization (FISH), and spectral karyotyping. Overall, the document provides an overview of common chromosomal abnormalities and the techniques used to identify them.

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

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

3. International system for
human cytogenetic
nomenclature.
eg- Xp21.2
Eg-47,XY,+21

4. 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

6. STRUCTURAL ABNORMALITIES
 Deletions-loss of a portion of chromosome
Eg-46,XY,del(16)(p11.2p13.1)

7. RING CHROMOSOME
Eg-46,XY,r(16)

8.  Insertion

9.  Inversion-2 breaks,turns upside down and re-attaches
Eg-inv(9)(p11q12)

10.  Isochromosome-one arm is lost,other arm is reduplicated

11.  Translocation-one segment transferred to another.
Eg-46,XY,t(2:5)(p12;q14)

13. CLINICAL
ABNORMALITIES

14. 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

15. 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

18. 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

19. 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

21. 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

24. CYTOGENETIC DISORDERS AFFECTING SEX
CHROMOSOME
 More common than autosomal aberrations.
 Lyon hypothesis

25. 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)

26.  Female, short stature, primary amenorrhea, sterility, spares hair and
underdeveloped breast
 Neonatal: wide spaced nipple, lymphedema , shield chest,

27. 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

29. 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)

30. KARYOTYPING
 3 main methods to identify chromosomes
 G BANDING-------giemsa
 Q BANDING-------quinacrine
 R BANDING-------reverse

31. 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

32. 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

34. 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

35. 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.

36. metaphase FISH interphase FISH

38. ADVANTAGES OF FISH
 Rapid
 High efficiency of hybridization and detection
 Lots of cells can be analyzed
 Cells do not have to be replicating

39. SPECTRAL KARYOTYPING
 Chromosomal and subchromosomal painting probes that make use
of sorted or microdissected chromosomes

41. 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.

42. THANK YOU