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

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

• 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

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

• 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























XX (or XY)

Sex Determination

female (XX)

male (XY)











The Y Chromosome
• Fewer than two dozen genes identified • One is the master gene for male sex
– 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


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)

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. “


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

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


galactose + glucose


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.

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.”


“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 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).

Complete and Sectoral Heterochromia

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

• 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

normal chromosome

one segment repeated
three repeats

A linear stretch of DNA is reversed within the chromosome

segments G, H, I become inverted

In-text figure Page 206

• 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

Philadelphia Karyotype

one chromosome

a nonhomologous chromosome

nonreciprocal translocation In-text figure Page 206

In-text figure

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

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

• 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




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


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


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


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

Sign up to vote on this title
UsefulNot useful