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

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

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 dont 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

Mothers Age

Incidence/1000births Age = 35

Boy with Downs 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)

Turners 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

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