THE HUMAN CHROMOSOME

Chromosome

• Primarily consists of DNA and

protein

• Distinguished by size and shape

• Essential parts

• Telomeres

• Origins of replication sites

• Centromere

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Subtelomere

Karyotyping

Chromosome Chart

• Confirm a clinical diagnosis

• Reveal effects of environmental toxins
• Clarify evolutionary relationships

Nomenclature of Chromosome

• International System for Human Cytogenetic Nomenclature

• Autosomes are numbered from 1-22, as nearly as possible in descending order of length.

• Identification would be based on size, the position of centromere and other morphological
features

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Petit (p) – short arms

Queue (q) – long arms

Regions (p1, p2, p22 and q1, q22)

Bands (p1 1)

Sub-bands (p1 1.1)

46,XY,dup(14)(q22q25)

46, XX, del (14) (q23)

46, XX, r (7)(q22q36)

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Classes of Chromosome

Chromosome morphology

“Morphology” is the study of the forms of things.

For Chromosome, it is best determined during metaphase

Sister chromatids or Dyads are joined by the centromere

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Visualizing Chromosomes

• Tissue is obtained from person

• Fetal tissue

• Amniocentesis

• Chorionic villi sampling

• Fetal cell sorting

• Chromosome microarray analysis

• Adult tissue

• White blood cells

• Skin-like cells from cheek swab

Amniocentesis

• Fetus at 15–16 weeks

• Fetal cells suspended in the fluid around the fetus are

sampled

• Detects about 1000 of the more than 5000 known

chromosomal and biochemical problems.

Chorionic villus sampling

• Cells of the chorion are sampled

• Performed during 10–12th week of pregnancy

• Provides earlier results than amniocentesis

• Does not detect metabolic problems

• Has greater risk of spontaneous abortion

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Staining Chromosomes

• Dyes were used to stain chromosomes a uniform color

• Were grouped into decreasing size classes, designated A though G

• Improved staining techniques gave banding patterns unique to each chromosome

• Researchers found that synchronizing the cell cycle of cultured cells revealed even more bands
per chromosome

Viewing Chromosomes

FISH

Fluorescence in situ hybridization (abbreviated FISH) is a laboratory technique used to detect and
locate a specific DNA sequence on a chromosome. In this technique, the full set of chromosomes from
an individual is affixed to a glass slide and then exposed to a “probe”—a small piece of purified DNA
tagged with a fluorescent dye. The fluorescently labeled probe finds and then binds to its matching
sequence within the set of chromosomes. With the use of a special microscope, the chromosome and
sub-chromosomal location where the fluorescent probe bound can be seen.

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IDEOGRAM

Schematic chromosome map

Indicates chromosome arms (p or q) and major regions delineated by banding

patterns

Indirect Detection of Extra Chromosomes

• Maternal serum markers offer an indirect method.

• These are biochemicals whose levels are in a normal range in a woman carrying a fetus with a
normal number of chromosomes but lie outside the range with fetuses that have an extra copy
of a certain chromosome.

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Maternal Serum Markers for Trisomy 21

Cell-Free DNA Testing

• In the maternal blood are pieces of DNA from

the fetus.

• Up to 20 percent of these pieces come from

the placenta, and thus represent the fetal
genome.

• Testing DNA can detect certain fetal

chromosomal abnormalities, like some of the
trisomy conditions.

• The test can be performed at 10 weeks into

the pregnancy.

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Chromosomal abnormalities

Numerical abnormalities

Atypical Chromosome Number

Euploidy is the state of an individual possessing complete sets of chromosomes with none extra or
missing.

Numerical abnormalities involve gain or loss of complete chromosomes

a. Polyploidy

a condition in Aneuploidywhich the cells of an organism have more than one pair chromosomes.

b. Aneuploidy

the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47
chromosomes instead of the usual 46

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Trisomies

• Autosomal aneuploids cease developing as

embryos or fetuses.

• Frequently seen trisomies in newborns are

those of chromosomes 21, 18, and 13.

• Carry fewer genes than other

autosomes

Trisomy 21

• Down syndrome

• Most common trisomy among newborns

• Distinctive facial and physical problems

Trisomy 18

• Edwards syndrome

• Due to nondisjunction in meiosis II in oocyte and

generally do not survive

• Serious mental and physical disabilities

• Distinctive feature— Oddly-clenched fists

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Trisomy 13

• Patau syndrome

• Very rare and generally do not survive 6

months

• Serious mental and physical disabilities

• Distinctive feature—Eye fusion

How Nondisjunction Leads to Sex Chromosome Aneuploids

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Turner (XO) Syndrome

• One in 2500 female births

• 99% of affected fetuses die in utero

• Features:

• Short stature

• Webbing at back of neck

• Incomplete sexual development (infertile)

• Impaired hearing

• Individuals who are mosaics may have children

Triple X Syndrome

• One in 1000 female births

• Few modest effects on phenotype include tallness,

menstrual irregularities, and slight impact on intelligence

• X inactivation of two X chromosomes occurs and cells have

two Barr bodies

• May compensate for presence of extra X

Klinefelter (XXY) syndrome

• One in 500 male births

• Phenotypes include:

a. Incomplete sexual development

b. Rudimentary testes and prostate

c. Long limbs, large hands and feet

d. Some breast tissue development

• Common cause of male infertility

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XXYY Syndrome

• Arises due to unusual oocyte and sperm

• Associated with more severe behavioral problems than

Klinefelter syndrome

• AAD, obsessive compulsive disorder, learning

disabilities

• Individuals are infertile

• Treated with testosterone

Jacobs (XYY) Syndrome

• One in 1000 male births

• 96% are phenotypically normal

• Modest phenotypes

• Great height

• Acne

• Speech and reading disabilities

• Studies suggest increase in aggressive behaviors are not

supported

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Chromosome Structural Abnormalities

Deletions

• Missing genetic segment from a chromosome

• Often not inherited

• Rather they arise de novo

• Larger deletions increase the likelihood that there

will be an associated phenotype

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Deletion

a. Interstitial

• short arm of chromosome 4

• Wolf-Hirschhorn syndrome

b. Terminal
• end terminus of the long arm of
chromosome 11
• Jacobsen syndrome

Terminal
• short arm of chromosome 5
• Cri du chat (cat cry) syndrome

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Duplications

• Presence of an extra genetic segment on a chromosome

• Often not inherited

• Rather they arise de novo

• Effect on the phenotype is generally dependent on their size

• Larger duplications tend to have an effect, while

smaller ones do not

Duplication

• Gene encoding peripheral myelin protein 22 on

chromosome 17

• Charcot-Marie-Tooth Disease

• Inverted champagne bottle

Translocations

• Two nonhomologous chromosomes exchange segments

• Types:

• Robertsonian translocation

• Acrocentric chromosomes fuse together.

• This fusing joins two “long arms” of DNA into one.

• Reciprocal translocation

• occur when part of one chromosome is exchanged with another.

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Inversions

• Chromosome segment that is flipped in

orientation

• Paracentric inversion

• Pericentric inversion

• May impact meiotic segregation

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