Biology 311 Human Genetics
Fall 2006
Lecture 2: Chromosomes
Reading: Chapter 2 pp. 34-51
Outline:
1. Chromosome content
2. Chromosome structure
a. centromeres
b. origins
c. telomeres
3. Review of mitosis and meiosis
4. X-Y pairing in meiosis
5. Chromosome anatomy
a. size
b. centromere position
c. banding
d. new technologies
Lecture:
1. Chromosome content
humans
 diploid--2 copies of each gene
 # chromosomes = 46
 22 pairs of autosomes + 2 sex chromosomes XX or XY
life cycle (Fig. 2.2)
23, X
23, X or 23, Y
46, XY or 46, XX
23, X
23, X or 23, Y
egg (1n) + sperm (1n)  zygote (2n)  adult (2n) egg (1n) or sperm (1n)
fertilization
mitosis
meiosis
2. Chromosome structure
What are chromosomes? See Fig. 2.3
Higher levels of packing/organization:
DNA + histones nucleosomes  chromatin fiber  chromosome
Histones: basic proteins that help condense DNA, highly conserved in
eukaryotes
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Core histones: H2A, H2B, H3, H4
Histone H1 binds spacer region
Parts of a chromosome
a. centromere
 constriction on chromosome
 essential for cell division
 kinetochores form here
 microtubules link kinetochores to spindle poles during cell division
 specific DNA sequences form centromere
o yeast ~110 bp long (Fig. 2.5)
o mammals 100's of kilobases long, repetitive DNA
b. origins of replication
 defined in yeast by a genetic assay
 yeast origins are called "ARS" =autonomously replicating
sequence element (Fig. 2.5)
 in mammals, thought that many different types of sequences
can function as origins of replication
c. telomeres
 specialized structures at the end of chromosomes
 several functions
o stabilize ends of chromosomes
o make sure ends of chromosomes are replicated
o help position chromosomes in nucleus
 long array of tandem DNA repeats (Fig. 2.5)
 highly conserved sequence in evolution (humans=TTAGGG) at very end
 enzyme telomerase (made of RNA and protein) reproduces the ends
o RNA component of telomerase is primer (Fig. 2.6)
Two types of chromatin
Euchromatin: light staining R-bands that make up most of chromatin; exists in
extended state during interphase; has genes that can be expressed.
Heterochromatin: dark staining regions (G-bands) that are condensed
throughout the cell cycle; contains few expressed genes.
3. Mitosis and meiosis: review on your own
Know stages and events at each stage, especially regarding the genetic
material. Know relevant terms.
What are the similarities and differences between mitosis and meiosis?
(Table 2.2)
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4. X-Y pairing in meiosis
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females have two Xs that pair in meiosis
males have an X and a Y
how do these segregate properly?
o region of 2.6 megabases of homology between X and Y="major
pseudoautosomal region" that pairs during meiosis
o X-over required in region to maintain pairing
5. Studying human chromosomes



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human white blood cells used
grow in culture to obtain mitotic cells
use mitosis inhibitor (colcemid) that prevents completion of mitosis
preferable to have chromosomes in prometaphase (end of prophase,
beginning of metaphase)
chromosomes are identified based on
o size
o position of centromeres
o banding pattern
a. size
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humans have 23 pairs of chromosomes
autosomes are arranged in pairs from largest (#1) to smallest (#22),
followed by sex chromosomes
karyotype: chromosome makeup of an individual
human female: 46, XX
human male: 46, XY
b. centromere position
metacentric: chromosome has centromere in middle of chromosome
submetacentric: centromere in middle, but slightly offset
acrocentric: centromere is located closer to one end
telocentric: centromere is located at essentially the end of the chromosome
chromosome arms
p=petit, shorter arm of chromosome
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q=queue, longer arm of chromosome
c. banding pattern
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
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different stains give different banding patterns
most common
o G-banding (Fig. 2.14), Giemsa stain binds DNA. Q-bands=dark,
heterochromatin; R-bands=weak, euchromatin
o R-banding gives essentially the reverse of G-banding pattern
o Q-banding, quinacrine or other fluorescent stain gives same pattern
as Giemsa
Location of bands relative to centromere (Fig. 2.13)
o Bands: Q20 is closer to centromere than q21
o Subbands: q21.1 is closer to centromere than q21.2
http://www.ncbi.nlm.nih.gov/
Can identify structural changes 1-10 megabases in size
d. newer chromosome technologies (Fig. 2.16)
chromosome FISH: Fluorescence in situ hybridization
o Used to identify specific DNA regions on a chromosome
o Involves tagging a DNA probe and hybridizing to denatured
chromosomal DNA on slide
chromosome "painting"= New technology that enables each chromosome to
be visualized as a different color.
o Mixed probe: Many DNA sequences from the same chromosome
o Tag with different colored dyes
o Important technology for identifying chromosomal defects (translocations,
etc. Fig. 2.18) and rearrangements associated with certain cancers (Fig.
2.17)
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