CYTO Chromosome Aberrations

dicentric

two centromeres

acentric

lacking centromere

chromosome identification

by size, centromere position, and banding pattern

g banding

dark bands (condensed chromatin)

hetermochromatic

AT rich

euchromatic

gene rich

constitutional abnormality

chromosome abnormality present in all cells of the body

somatic or acquired abnormality

chromosome abnormality present only in certain cells/tissues

mosaic individual

one who posses two or more genetically different cell lines derived from single zygote

Deletion

terminal deletion - sa dulo

intercalary deletion - middle, in between, or inside

Wolf-Hirschhorn

deletion: 4p16.3

• severe growth retardation

• midline facial defects

• mental retardation

• small head

• prominent frontal lobe

• between eyebrows

• cleft lip/palate

• cardiac defects

• wide-spaced eyes

• broad nasal bridge

Cri du chat

deletion: 5p12.2

• eerie cry (high pitched cry)

• wide-spaced eyes

• small chin

• small head

• round face

• severe psychomotor

• mental retardation

Langer-Giedion

deletion: 8q24.11-q24.13

• cauliflower ears

• small head'

• mental retardation

• sparse hair

• bulbous nose

• short stature

• multiple cartilaginous growth on bone surface

Williams

microdeletion: 7q11.23

• cardiac anomalies

• mental retardation

• characteristic facies - facial features distinct to certain conditions

• growth retardation

• gregarious disposition - overly friendly; high level of empathy with anxiety

• connective-tissue problems

WAGR

microdeletion: 11p13

• kidney tumor - Wilm’s Tumor/nephroblastoma

• absence of iris - Aniridia

• genital abnormalities - 

  • male: cryptorchidism

  • female: non-functional ovaries

• growth retardation

Prader Willi

microdeletion: 15q11.2

• developmental delay

• mental retardation

• decreased muscle tone

• obesity small genitals

• excessive appetite

• hypopigmentation

Angelman

microdeletion: 15q11.2

• developmental delay

• mental retardation

• unstable gait

• absence of speech

• hyperactivity

• spontaneous laughter

• hypopigmentation

Miller-Dieker

microdeletion: 17p13.3

• smooth brain - cerebral cortex smooth

• small head

• small chin

• growth failure

• cardiac abnormalities

Smith- Magenis

microdeletion: 17p11.2

• flat midface

• wide head

• broad nasal bridge

• short fingers and toes

• mental retardation

• hyperactivity

• short stature

• characteristic of behavioral problems

Alagille

microdeletion: 20p11.23-p12.2

• chronic bile flow suppression

• dysmorphic facies

• ring-like corneal opacity

• vertebral arc defects

• narrowing of heart opening

catch 22

microdeletion: 22q11.2

• cardiac defects

• abnormal facies

• underdeveloped thymus

• cleft palate

• decreased calcium in blood

CATCH acronym

cardiac defect

abnormal faces

thymic hypoplasia

cleft palate

hypocalcemia

DiGeorge Syndrome

microdeletion: 22q11.2

• underdeveloped thymus and parathyroid glands

• facial abnormalities

• cardiac defects

Velocardiofacial

microdeletion: 22q11.2

• cleft palate

• abnormal nose

• developmental delay

• cardiac abnormalities

Inversion

Paracentric - centromere not part of rearranged segment

• inv(10)(p11-p13)

pericentric - centromere part of rearranged segment

• inv(10)(p13q15)

inv(9)(p12q13)

- pericentric

• most common inversion in humans

• no harmful effects

• could lead to risk miscarriage/infertility

Duplication

result of unequal crossing over between synapse chromosomes during or through replication

error to meiosis

Beckwith-Wiedemann

duplication: 11p15.5

• large tongue

• tissue and organ overgrowth

• mild mental retardation

Charcot-Marie-Tooth disease Type 1A

duplication: 17p11.2-p12

• decreased reflexes

• progressive distal muscular wasting (distal myopathy)

• weakness of distal muscles: lower arms, legs, hands, feet

• decreased muscle tone

• sensory neuropathy

cat-eye

duplication: 22pter-q11.2 (telomere included)

• eye defects

• absence of anal opening

• skin tags in front of ears

• characteristics facies

• renal, skeletal, genital abnormalities

• mental retardation

Translocation

structural rearrangement involving two nonhomologous chromosome (chromosome 9 and chromosome 22)

most cases, no loss or gain of chromosomal material during exchange

2 types of Translocation

• reciprocal translocation - exchange between nonhomologous chromosome, regardless of location of centromere

• Robertsonian translocation - exchange between nonhomologous chromosomes but centromeres are both acrocentric

Chromosome 14 robertsonian translocation group

included in group D (medium-sized acrocentric centromere)

chromosome 21 robertsonian translocation group

Down Syndrome

included in group G (very short acrocentric centromere)

Philadelphia chromosome

seen with px w chronic myeloid leukemia

• translocation in chromosome 9 and chromosome 22; q34;q11.2

chromosome 9 reciprocal translocation group

group C (6-12; medium-sized with submedian centromere)

chromosome 22 reciprocal translocation group

Group D (acrocentric centromere)

Ring Chromosome

two arms have been fused together to form a ring

ring chromosome 20

epilepsy

ring chromosome 13 and 14

retardation or intellectual disability

dysmorphic facial features

ring chromosome 15

mental retardation

dwarfism

microcephaly - baby’s head is smaller compared to others

ring chromosome X (x-linked)

turner syndrome

isochromosome

symmetrical chromosomes

sometimes seen in females with turner syndrome or in tumor cells

common cause: chromosome divide along incorrect plane during meiosis

sex aneuploidies

disease caused by abnormal number of sex chromosomes

44 + XXY

Klinefelter’s syndrome (male have extra X chromosome)

44 + XYY or double Y syndrome

Jacob syndrome (additional Y)

44 + X

turner’s syndrome (woman lack x choromosome)

holandric genes

inherited exclusively through male descent, transmitted through genes located on Y chromosome

sex-limited genes

genes present in both sexes but expressed only in one sex having hormonal determiner (activator)

cause sexual dimorphism

examples:

• beard in males

• milk in females

sex-linked inheritance

traits carried in either X or Y chromosome

more males (XY) develop traits than females (XX) 

examples:

• sickle cell anemia

• color blindness

sex-influenced traits

autosomal traits influenced by sex

occur only in autosomes

example:

• baldness

x-linked recessive

more males than females are affected

skip generations

x-linked dominant

affected males produce all affected female offspring and no affected male offspring

y-linked inheritance

trait passed from father to son

only males are affected

Holandric genes

samples for karyotyping analysis

adult: blood, skin, bone marrow

unborn child : amniotic fluid, extraembryonic cells

lectins

mitotic agents stimulate mitosis

colchicine

mitotic inhibitor; arrest mitosis at metaphase

hypotonic solution

provide more room for chromosome to spread out and allows for clearer visualization during karyotyping.

checked in karyotyping

length of chromosome arms

position of centromere

shape and general appearance of chromosome

size and placement of bands

other anomalies and chromosome aberrations

euploidy

complete set of chromosome present

aneuploidy

loss or gain of one chromosome

• monosomy - loss of 1 chromosome

• trisomy - gain of 1 chromosome

polyploidy

more than 2 set of chromosome is present (1 set = 23 chromosome)

• triploid - 3 sets (69 chromosome)

  • most common form that cause spontaneous abortions (15-18%)

  • two sets of paternal chromosomes because of polyspermy

• tetraploid - 4 sets (92 chromosome)

  • 5% spontaneous abortions

  • failure of cytokinesis

nondisjunction

from random error during production of gametes

failure of homologs or sister chromatids

produce abnormal gametes

karyotyping stain

giemsa after solution of colchicine

barr body

sex chromatin body

female = 1 barr

male = no barr

Murray Barr

discovered barr body; inactive x chromosome in female somatic cell

lyonization

inactivation of sex chromosome, transforming it into a Barr body

chromosome group A

1-3, largest, median centromere

chromosome group B

4-5, large, submedian centromere

chromosome group C

6-12, medium-sized, submedian centromere

chromosome group D

13-15, medium-sized acrocentric centromere

chromosome group E

16-18, short, can be median or submedian

chromosome group F

19-20, short, median centromere

chromosome group G

21-22, very short, acrocentric centromere

chromosome X group

same with Group C

Chromosome Y group 

same with Group G

differences in basic number of chromosome 

due to successive unequal translocations which will finally remove alll essential genetic material from the chromosomes, leading to abnormalities.

differences in position of centromeres

brought by translocations

differences in number and position of satellites

small bodies attached to chromosome by a thin thread

differences in relative size of chromosome

caused by segmental interchange of unequal lengths

differences in degree and distribution of heterochromatic regions

stains darker euchromatin indicates tighter packing

G banding

giemsa stain

digestion of chromosome with trypsin

300-400 bands in human genome

g banding procedure

1. de stain slides for 10 mins with 95% ethanol (fixative)

2. place slide in phosphate buffer solution and incubate for 10 minutes at 56C

3. treat slide with 0.22ml of 25% trypsin, 2.5ml methanol, 0.22ml stock giemsa, 6.6ml PBS, pH=7.4

4. flood slide with stain solution for 15mins, rinse with water and airdry

5. view under bright field, OIO

Q banding

quinacrine

binds to adenine-thymine rich regions

classic karyotyping

R banding

“reverse” giemsa

dark guanine-cytosine rich region

hightemp, low pH, acridine orange stain

determine deletions

c banding 

centrometric 

giemsa binds with heterochromatin

use alkali solution (barium hydroxide)

t banding

visualize telomeres

silver staining

silver nitrate

stains nucleolar organization region-associated protein (NOR)

located in satellite stalk of acrocentric centromere

spectral karyotyping

SKY

visualize all pairs of chromosomes in an organism in different colors