Chromosomes and Human Genetics

Chromosomes & Cancer
• Some genes on chromosomes control cell
growth and division

• If something affects chromosome

structure at or near these loci, cell division may spiral out of control

• This can lead to cancer

Philadelphia Chromosome
• First abnormal chromosome to be
associated with a cancer

• Reciprocal translocation • Causes chronic myelogenous leukemia
(CML)

Genes
• Units of information about heritable traits • In eukaryotes, distributed among
chromosomes

• Each has a particular locus
– Location on a chromosome

Homologous Chromosomes
• Homologous autosomes are identical in
length, size, shape, and gene sequence • Sex chromosomes are nonidentical but still homologous • Homologous chromosomes interact, then segregate from one another during meiosis

Alleles
• Different molecular forms of a gene • Arise through mutation • Diploid cell has a pair of alleles at each
locus

• Alleles on homologous chromosomes may
be same or different

Sex Chromosomes
• Discovered in late 1800s • Mammals, fruit flies
– XX is female, XY is male

• In other groups XX is male, XY female

• Human X and Y chromosomes function as
homologues during meiosis

Karyotype Preparation Stopping the Cycle
• Cultured cells are arrested at metaphase
by adding colchicine

• This is when cells are most condensed and
easiest to identify

Karyotype Preparation
• Arrested cells are broken open • Metaphase chromosomes are fixed
and stained

• Chromosomes are photographed
through microscope

• Photograph of chromosomes is cut
up and arranged to form karyotype diagram

Karyotype Diagram

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

XX (or XY)

Sex Determination

female (XX)

male (XY)

eggs

sperm

X X

x
x

Y X

X X XX

X XX

Y

XY

XY

The Y Chromosome
• Fewer than two dozen genes identified • One is the master gene for male sex
determination
– SRY gene (sex-determining region of Y)

• SRY present, testes form • SRY absent, ovaries form

Effect of Y Chromosome

appearance of structures that will give rise to external genitalia

appearance of “uncommitted” duct system of embryo at 7 weeks

7 weeks Y present Y absent Y present Y absent

testes 10 weeks

ovaries

ovary testis

birth approaching

Androgen Deprivation
• The “Guevedoces” of the Dominican
Republic • Reports from isolated villages asserted that ”children appearing to be girls

turned into men at puberty.”

(Urological Sciences Research Foundation)
• http://www.usrf.org/news/010308-guevedoces.html

Male Pseudohermaphrodites
• “These children appeared to be girls at
birth, but at puberty these 'girls' sprout muscles, testes, and a penis. For the rest of their lives they are men in nearly all respects …. Their underlying pathology was found to be a deficiency of the enzyme, 5-alpha Reductase. “

Map

From the American Journal of Medicine (Am. L. Med. 62: 170-191, 1977)

From the American Journal of Medicine (Am. L. Med. 62: 170-191, 1977)

From the American Journal of Medicine (Am. L. Med. 62: 170-191, 1977)
• 6. And for the rest of their lives, the guevedoces
resemble the other Dominican men in all respects except: * Beard growth is scanty. * There is no hairline recession. * None has acne. * The prostate remains small

The X Chromosome
• Carries more than 2,300 genes
• Most genes deal with nonsexual traits • Genes on X chromosome can be
expressed in both males and females

Genetic Abnormality
• A rare, uncommon version of a trait • Polydactyly
– Unusual number of toes or fingers – Does not cause any health problems

– View of trait as disfiguring is subjective

New Bond Girl Proud of Her 'Little Oddity‘ by Jonathan Crow |
October 7 , 2008
“Gemma Arterton … has proven herself to be exceptional not only for her English Rose beauty, but also because she was born with six fingers on each hand.”

Genetic Disorder
• Inherited conditions that cause mild to
severe medical problems

• Why don’t they disappear?
– Mutation introduces new rare alleles – In heterozygotes, harmful allele is masked, so it can still be passed on to offspring

Autosomal Recessive Inheritance Patterns
• If parents are
both heterozygous, child will have a 25% chance of being affected
Figure 12.10a

Page 204

Galactosemia
• Caused by autosomal recessive allele • Gene specifies a mutant enzyme in the
pathway that breaks down lactose
enzyme 1 enzyme 2 enzyme 3

lactose

galactose + glucose

galactose-1phosphate

galactose-1phosphate intermediate in glycolysis

In-text figure Page 204

One Common Ancestor Behind Blue Eyes
• People with blue eyes have a single,
common ancestor, according to new research. • A team of scientists has tracked down a genetic mutation that leads to blue eyes. The mutation occurred between 6,000 and 10,000 years ago. Before then, there were no blue eyes.

http://www.livescience.com/health/080131-blue-eyes.html

Percentage Frequency of Light Eyes in and Near Europe

from Beals et al., An Introduction to Anthropology, 1965

Danish geneticist Hans Eiberg in the journal Human Genetics
• “Originally, Eiberg says, everyone in the
world had brown eyes. But the mutation acts as a switch that shuts off the OCA2 gene, which controls the eye's production of melanin. Melanin is the pigment that gives color to eyes and hair.”

• http://www.spiegel.de/international/world
/0,1518,532346,00.html

“Inbred Mutants”
“Brad Pitt's squinting a bit in the light of the flashbulbs, but he has blue eyes. A new study suggests he shares a common ancestor with all the world's other blue-eyed denizens.”

Pitt, Diaz, and Sinatra

Heterochromia
• Heterochromia is an ocular condition in
which one iris is a different color from the other iris (complete heterochromia), or where the part of one iris is a different color from the remainder (partial heterochromia or sectoral heterochromia).

http://en.wikipedia.org/wiki/Eye_color

Complete and Sectoral Heterochromia

Causes of Heterochromia
• Chimeras and Waardenburg
syndrome • Injury or medication

Duplication
• Gene sequence that is repeated several to
hundreds of times

• Duplications occur in normal chromosomes • May have adaptive advantage
– Useful mutations may occur in copy

Duplication
normal chromosome

one segment repeated
three repeats

Inversion
A linear stretch of DNA is reversed within the chromosome

segments G, H, I become inverted

In-text figure Page 206

Translocation
• A piece of one chromosome becomes
attached to another nonhomologous chromosome • Most are reciprocal • Philadelphia chromosome arose from a reciprocal translocation between chromosomes 9 and 22

Philadelphia Chromosome

http://gslc.genetics.utah.edu/units/disorders/karyotype/reciprocal.cfm

Philadelphia Karyotype

http://gslc.genetics.utah.edu/units/disorders/karyotype/reciprocal.cfm

Translocation
one chromosome

a nonhomologous chromosome

nonreciprocal translocation In-text figure Page 206

In-text figure

Deletion
• Loss of some segment of a chromosome • Most are lethal or cause serious disorder

Aneuploidy
• Individuals have one extra or less
chromosome • (2n + 1 or 2n - 1) • Major cause of human reproductive failure • Most human miscarriages are aneuploids

Polyploidy
• Individuals have three or more of each
type of chromosome (3n, 4n)

• Common in flowering plants • Lethal for humans
– 99% die before birth – Newborns die soon after birth

Nondisjunction
n+1

n+1

n-1

chromosome alignments at metaphase I

n-1 nondisjunction alignments at at anaphase I metaphase II anaphase II Figure 12.17 Page 208

Down Syndrome
• Trisomy of chromosome 21 • Mental impairment and a variety of
additional defects

• Can be detected before birth • Risk of Down syndrome increases
dramatically in mothers over age 35

Trisomy 21

Non-disjunction

Karotype Trisomy 21

Mother’s Age

Incidence/1000births Age = 35

Boy with Down’s Syndrome

Turner Syndrome
• Inheritance of only one X (XO) • 98% spontaneously aborted • Survivors are short, infertile females
– No functional ovaries – Secondary sexual traits reduced

– May be treated with hormones, surgery

Monosomy (Having only one X chromsome per cell)

Turner’s Syndrome

Klinefelter Syndrome
• XXY condition • Results mainly from nondisjunction in
mother (67%) • Phenotype is tall males
– Sterile or nearly so – Feminized traits (sparse facial hair, somewhat enlarged breasts) – Treated with testosterone injections

Klinefelter

http://www.tokyo-med.ac.jp/genet/index-e.htmo

XYY Condition
• Taller than average males • Most otherwise phenotypically normal • Some mentally impaired • Once thought to be predisposed to
criminal behavior, but studies now discredit

Phenotypic Treatments
• Symptoms of many genetic disorders can
be minimized or suppressed by
– Dietary controls – Adjustments to environmental conditions – Surgery or hormonal treatments

Genetic Screening
• Large-scale screening programs detect
affected persons

• Newborns in United States routinely
tested for PKU
– Early detection allows dietary intervention and prevents brain impairment

Prenatal Diagnosis
• Amniocentesis
• Chorionic villus sampling • Fetoscopy • All methods have some risks

Amniocentesis

Pedigree Analysis

Preimplantation Diagnosis
• Used with in-vitro fertilization • Mitotic divisions produce ball of 8 cells • All cells have same genes • One of the cells is removed and its
genes analyzed

• If cell has no defects, the embryo is
implanted in uterus

Preimplant Diagnosis

http://www.layyous.com/book/book%20images/Untitled-196b.jpg

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