Genet 302 lec 6 & 7
When was the correct human chromosome number established and by whom?
1956 by Joe Hin Tjio and Albert Levan. They showed humans have 46 chromosomes, correcting the earlier incorrect count of 48.
How are human chromosomes classified by centromere position?
Metacentric – centromere in middle
Acrocentric – centromere near one end
Humans have metacentric and acrocentric, but not telocentric chromosomes.
What is ISCN and why is it important?
The International System for Human Cytogenetic Nomenclature (est. 1960, Denver).
It standardizes how we write and interpret karyotypes worldwide. Updated every ~3 years.
What is Step 1 of human karyotyping?
Use white blood cells (WBCs) to create a metaphase chromosome spread (chromosomes are condensed and visible).
What is a karyogram?
A photograph of metaphase chromosomes arranged in standard order by size, centromere position, and banding pattern.
What is a karyotype?
A written statement describing:
Total chromosome number
Sex chromosomes
Any abnormalities
Example: 46,XX or 47,XY,+21
What must you be able to do for simple chromosome abnormalities (exam skill)?
Draw chromosomes from a given karyotype
Write a karyotype from given chromosomes
What causes chromosome number abnormalities?
Non-disjunction – failure of chromosomes to separate properly.
During which stages can nondisjunction occur?
Anaphase of mitosis
Anaphase I of meiosis
Anaphase II of meiosis
What is euploidy?
Normal chromosome number (e.g., 46,XX or 46,XY).
What is trisomy?
Presence of one extra chromosome (2n + 1).
Example: 47,XX,+21 (Down syndrome).
What is triploidy?
Entire extra set of chromosomes (3n = 69 total).
What is Turner syndrome?
45,X
Female with only one X chromosome (monosomy X).
What is Klinefelter syndrome?
47,XXY
Male with an extra X chromosome.
What do + and – mean in karyotype notation?
+ = extra chromosome
– = missing chromosome
Example: 47,XY,+21
What is mosaicism?
Presence of two or more different karyotypes in one individual.
Written using “/”
Example: 45,X / 46,XX
What is a chromosome map?
A simplified diagram representing banding patterns seen under a microscope.
What is the centromere constriction?
The primary constriction present on all chromosomes that separates p and q arms.
Which chromosomes have a secondary constriction due to 45S rRNA genes?
Chromosomes 13, 14, 15, 21, and 22 (acrocentric chromosomes).
What are chromosome arms?
p arm = short arm (petite)
q arm = long arm
What creates chromosome bands?
Giemsa staining (G-banding).
What is the difference between Giemsa dark and light bands?
Dark bands: AT-rich, gene-poor, low GC content
Light bands: GC-rich, gene-rich
What is a band?
Any distinguishable stained region on a chromosome.
Why are bands not named in simple order (1,2,3,4)?
Because higher-resolution preparations reveal more sub-bands, so the system must be flexible.
How are chromosome regions numbered?
Numbered from the centromere outward toward each end on both p and q arms.
Explain 18p11.2
18 = chromosome number
p = short arm
1 = region 1
1 = band 1
.2 = sub-band 2
What does 5q12 mean?
Chromosome 5, long arm (q), region 1, band 2.
Define these terms: p, q, cen, pter, qter.
p = short arm
q = long arm
cen = centromere
pter = end of short arm
qter = end of long arm
How would you systematically read a full karyotype?
Total chromosome number
Sex chromosomes
Numerical abnormalities (+/–)
Structural abnormalities (if present)
Mosaicism (if “/” present)
define: del, dup, inv, t
del = deletion
dup = duplication
inv = inversion
t = translocation
define: mat, pat, der, mar.
mat = maternal origin
pat = paternal origin
der = derivative chromosome (from translocation; named by centromere)
mar = marker chromosome (unidentified abnormal chromosome)
How are single-break rearrangements described?
List the chromosome and the breakpoint.
Example: terminal deletion.
interpret: 46,XX,del(5)(p14.1)
Female with 46 chromosomes; deletion on chromosome 5 at band p14.1 (Cri-du-chat syndrome).
What is a terminal deletion?
A break near the end of a chromosome with loss of the distal segment.
How are two-break rearrangements on the same arm written?
List the breakpoint closest to the centromere first.
What is an interstitial deletion?
Two breaks on same arm; internal segment removed and ends rejoin.
What deletion causes Prader–Willi syndrome (PWS)?
Deletion on paternal chromosome 15 between 15q11 and 15q23.
Example: 46,XY,del(15)(q11q23)pat
How are inversions involving both arms written?
List p-arm breakpoint first, then q-arm.
Which notation correctly describes a pericentric inversion?
46,XX,inv(2)(p12q21)
(Pericentric = includes centromere)
Difference between pericentric and paracentric inversion?
pericentric: includes centromere (p + q arms)
Paracentric: same arm only (no centromere)
How are translocations between chromosomes written?
List chromosomes in order: X, Y, 1, 2, 3…
interpret: 46,XX,t(1;9)(p35;p21)
Female with reciprocal translocation between chromosome 1 (p35) and chromosome 9 (p21).
What is a reciprocal translocation?
Exchange of segments between two non-homologous chromosomes.
What is a derivative chromosome?
An abnormal chromosome formed by translocation, named by the chromosome that provides the centromere.
Why is a chromosome called der(1)?
Because it contains the centromere of chromosome 1.
What is a marker chromosome (mar)?
An abnormal chromosome whose origin cannot be identified by standard karyotyping.
Where do marker chromosomes commonly originate?
Often from p arm + centromere of acrocentric chromosomes (13,14,15,21,22).
interpret: 47,XX,+mar
Female with an extra unidentified marker chromosome.
How do you write a person homozygous for a rearrangement?
List the rearrangement twice, separated by commas.
Example: 46,XX,inv(2),inv(2)
How are complex karyotypes written?
List abnormalities in chromosome order: X, Y, 1, 2, 3…
interpret: 45,X,inv(2),del(5)
45 chromosomes (missing one X → Turner)
Inversion on chromosome 2
Deletion on chromosome 5
What are the two types of deletions?
Terminal deletion
Interstitial deletion
What are the two types of duplications?
Tandem duplication (adjacent repeat)
Insertional duplication (inserted elsewhere)
What are the two types of translocations?
Reciprocal translocation
Robertsonian translocation (fusion of two acrocentric chromosomes; small fragment lost)
What happens in a Robertsonian translocation?
Two acrocentric chromosomes fuse at centromeres → form one metacentric chromosome; short arms usually lost.
What must you be able to do for the exam (rearrangements)?
Draw simple rearrangements
Write correct karyotypes
Interpret breakpoints
Recognize inversion vs deletion vs translocation