14 chromosome and human genetics[revised]

7/25/2019 14 Chromosome and Human Genetics[REVISED]

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Chromosomes and

Human Genetics


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Chromosomes & Cancer

Some genes on chromosomes controlcell growth and division

If something affects chromosomestructure at or near these loci, cell

division may spiral out of control

This can lead to cancer


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Philadelphia Chromosome

First abnormal chromosome to be

associated with a cancer

Reciprocal translocation

Causes chronic myelogenous leukemia

(CML)


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Genes

Units of information about heritable

traits

In eukaryotes, distributed among

chromosomes

Each has a particular locus

Location on a chromosome


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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


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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


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Chromosomes: A review

Humans have 46 chromosomes that are in 23 pairswithin a cells nucleus

Pairs of chromosomes are called homologous chromosomes

Autosomes are the 22 pairs of chromosomes that control traitsthat do not relate to gender of an individual

Sex chromosomes are the 1 pair that contains the genes that docontrol gender

Cells (body cells) that have 46 (2N) chromosomes are

called diploid

Cells (sex cells) that have only 23 (N) chromosomes notin pairs are called haploid

18.1 Chromosomes


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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


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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


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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


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What is a karyotype?18.1 Chromosomes

Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

The 46 chromosomes of a male

sister

chromatids

centromere

sex chromosomes

in males

homologous

autosome pair

CNRI/SPL/Photo Researchers, Inc.


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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)

Figure 12.4Page 197

Karyotype Diagram


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Sex

Determination

X

X Y

X

XX

XY

XX

XY

X X

Y

X

x

x

eggs sperm

female(XX)

male(XY)

Figure 12.5Page 198


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The Y Chromosome

Fewer than two dozen genes identified

One is the master gene for male sexdetermination

SRY gene (sex-determining region of Y)

SRY present, testes form

SRY absent, ovaries form

appearance of structures appearance of


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Effect of Y

Chromosome

10 weeks

Y

present

Y

absent

7 weeks

birth approaching

appearance of structures

that will give rise to

external genitalia

appearance of

uncommitted duct system

of embryo at 7 weeks

Y

present

Y

absent

testis

ovary

testes ovaries

Figure 12.6Page 199


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The X Chromosome

Carries more than 2,300 genes

Most genes deal with nonsexual traits

Genes on X chromosome can beexpressed in both males and females


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Discovering

Linkage

homozygous dominantfemale

recessive male

Gametes:

XX X Y

All F1have red eyes

x

1/4

1/4

1/4

1/4

1/2

1/2 1/2

1/2

F2generation:

XX X Y

xGametes:

Figure 12.7

Page 200


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Linkage Groups

Genes on one type of chromosome

Fruit flies 4 homologous chromosomes

4 linkage groups

Not all genes on chromosome aretightly linked


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Full Linkage

x

AB ab

50% AB 50% ab

All AaBb

meiosis, gamete formation

Parents:

F1 offspring:

Equal ratios of two

types of gametes:

AB

ab

A

B

ab

ab

AB

Figure 12.8aPage 201


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Incomplete Linkage

Parents:

F1 offspring:

Unequal ratios of four

types of gametes:

All AaCc

x

meiosis, gamete formation

AC ac A

C A

C

A

C

a

c

a

c

A

c

a

C

a

c

parental

genotypes

recombinant

genotypes Figure 12.8bPage 201


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Crossover Frequency

Proportional to the distance that

separates genes

A B C D

Crossing over will disrupt linkage between

A and B more often than C and D

In-text figure

Page 201


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Linkage Mapping in Humans

Linkage maps based on pedigree

analysis through generations

Color blindness and hemophilia are very

closely linked on X chromosome


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Pedigree

Symbols

male

female

marriage/mating

Individual showing trait

being studied

sex not specified

generationI, II, III, IV...

offspring in order of birth,

from left to right



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Pedigree for Polydactyly

I

II

III

IV

V

6 7

12

5,5

6,6

5,5

6,6

5,5

6,6

5,5

6,6

5,5

6,6

5,5

6,6

6,6

5,5

6,6

5,5

5,6

6,7

6,6

6,6*Gene not expressed in this carrier.

*

malefemale

Figure 12.9b

Page 202


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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


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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


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Autosomal Recessive

Inheritance Patterns If parents are

bothheterozygous,

child will have a

25% chance ofbeing affected


20 3 Inheritance of genetic disorders


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Autosomal recessive disorder Individuals must be homozygous recessive to

have the disorder

20.3 Inheritance of genetic disorders


II

III

IV

Iaa A?

A?

A?A?Aa

A?aaaa

Aa

* relatives

Aa

Key

= affected

Aa = carrier (unaffected)

AA = unaffectedA? = unaffected

(one allele unknown)

aa

AaA?

Autosomal recessive disorders

Affected children can have

unaffected parents.

Heterozygotes (Aa) have an unaffected phenotype.

Two affected parents will always have affected children.

Affected individuals with homozygous unaffected mates will have

unaffected children.

Close relatives who reproduce are more likely to have

affected children.

Both males and females are affected with equal frequency.


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Galactosemia

Caused by autosomal recessive allele

Gene specifies a mutant enzyme in the

pathway that breaks down lactose

In-text figurePage 204

galactose-1-

phosphate

enzyme 2

lactose galactose

enzyme 1

+glucose

galactose-1-phosphate

enzyme 3

intermediatein glycolysis


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Autosomal

Dominant Inheritance

Trait typically

appears inevery

generation

Figure 12.10bPage 204

20 3 Inheritance of genetic disorders


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Autosomal dominant disorder Individuals that are homozygous dominant and

heterozygous will have the disorder



aa = unaffected(one allele unknown)= affected

= affected

= affectedAA

Aa

A?Autosomal dominant disorders

Affected children will usually have

an affected parent. Heterozygotes (Aa) are affected.

Two affected parents can produce an unaffected child.

Two unaffected parents will not have affected children.

Both males and females are affected with equal frequency.

III

II

I Aa Aa

aa Aa

*A? aa aa aa

aaaaaaaaAaAa

Key



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Genetic disorders of interest

Tay-Sachs disease: lack of the enzyme that breaks down lipids inlysosomes resulting in excess and eventually death of a baby

Cystic fibrosis: Cl- do not pass normally through a cell membraneresulting in thick mucus in lungs and other places often causinginfections

Phenylketonuria (PKU): lack of an enzyme needed to make a certainamino acid and affects nervous system development

Sickle-Cell disease: red-blood cells are sickle shaped rather than

biconcave that clog blood vessels

Huntington disease: huntington protein has too many glutamineamino acids leading to the progressive degeneration of brain cells




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Genetic disorders20.3 Inheritance of genetic disorders


many neurons in

normal brain

loss of neurons in

huntington brain


(both brain tissue slides): Courtesy Dr. Hemachandra Reddy, T he Neurological Science Institute, Oregon Health

& Science University; (woman with Huntington): Steve Uzzell


thick mucus

defective

channel

H2O

H2O ClCl Cl

H2OClCl

nebulizer

percussion

vest

Pat Pendarvis


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Huntington Disorder

Autosomal dominant allele

Causes involuntary movements, nervous

system deterioration, death

Symptoms dont usually show up until person

is past age 30

People often pass allele on before they knowthey have it


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Achondroplasia

Autosomal dominant allele

In homozygous form usually leads to

stillbirth

Heterozygotes display a type of dwarfism

Have short arms and legs relative to otherbody parts

20.5 Sex-linked inheritance


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Sex-linked inheritance

Traits are controlled by genes on the sexchromosomes

X-linked inheritance: the allele is carried on

the X chromosome Y-linked inheritance: the allele is carried on

the Y chromosome

Most sex-linked traits are X-linked


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X-Linked Recessive

Inheritance Males show

disorder morethan females

Son cannot inherit

disorder from his

father

Figure 12.12a

Page 205


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X-linked inheritance: Color blindness

Cross:

XBXb x XBY

Possible offspring:

XBXB normal vision female

XBXb normal vision female

XBY normal vision male

XbY normal vision male


Parents

Key

XB = Normal visionXb = Color-blind

Normal visionColor-blind

Phenotypic Ratio

Females All

Males 1:1 1

1XbYXBY

XBXbXBXB

XbXB

XB

Y

eggs

XBY XBXb

Offspring

sp

erm



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X-linked disorders

Key

XBXB = Unaffected female

XBXb = Carrier female

XbXb = Color-blind female

XBY = Unaffected male

XbY = Color-blind maleX-linked Recessive

Disorders

More males than females are affected.

An affected son can have parents who have the

normal phenotype.

For a female to have the characteristic, her father

must also have it. Her mother must have it or be a

carrier.

The characteristic often skips a generation from the

grandfather to the grandson.

If a woman has the characteristic, all of her sons willhave it.

grandson

daughter

grandfatherXBXB

XBY XBXb XBY XbXb

XbY

XbYXBY XBXB XBXb

XbY




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X-linked disorders: HemophiliaCopyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Unaffected male

Hemophiliac male

Unaffected female

Carrier female

??

??

??

Nicholas IIAlexandra

Olga

All were assassinated

Anastasia

Philip

Harry

Juan Carlos

Elizabeth II

Marie Alexi 9

5

12 13 16 14 15

6

3 4 7 8Mary

Alice1 2 10Louis IV

2. Edward VII

3. Irene

4. George V

6. Margaret

9. Juan

12. Diana

14. Edward

16. Sarah

Leopold Beatrice Helena

Albert

Edward

? ? ?

?

1. Victoria

7. Victoria

8. Alfonso XIII

Tatiana

Victoria

Victoria

11

10. Alexandra

11. Charles

13. Andrew

15. Anne


(queen): Stapleton Collection/ Corbis; (prince): Huton Archive/Getty Images

William


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Fragile X Syndrome

An X-linked recessive disorder

Causes mental retardation

Mutant allele for gene that specifies a

protein required for brain development

Allele has repeated segments of DNA


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Hutchinson-Gilford Progeria

Mutation causes accelerated aging

No evidence of it running in families

Appears to be dominant

Seems to arise as spontaneous

mutation

Usually causes death in early teens

18.6 Chromosome inheritance


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Changes in chromosome structure

Deletions loss of a piece of the chromosome (e.g.,Williams syndrome)

Translocations movement of chromosome segmentsfrom one chromosome to another nonhomologouschromosome (Alagille syndrome)

Duplications presence of a chromosome segmentmore than once in the same chromosome

Inversions a segment of a chromosome is inverted180 degrees


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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


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Duplication

normal chromosome

one segment

repeated

three repeats


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Inversion

A linear stretch of DNA is reversed

within the chromosome

segments

G, H, I

become

inverted

In-text figurePage 206


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Translocation

A piece of one chromosome becomes

attached to another nonhomologous

chromosome Most are reciprocal

Philadelphia chromosome arose from a

reciprocal translocation betweenchromosomes 9 and 22


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In-text figure

Page 206

Translocation

one chromosome

a nonhomologous

chromosome

nonreciprocal translocation

In-text

figurePage 206


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Deletion

Loss of some segment of a chromosome

Most are lethal or cause serious disorder



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Changes in chromosome structure


a

b

c

d

e

f

g

a

b

c

d

e

f

g

a

b

c

d

e

f

g

h

l

m

n

o

p

q

r

a

b

c

d

e

f

g

h

l

m

n

o

p

q

r

a

b

c

d

e

f

g

a

b

c

d

e

d

e

f

g

+

a

b

c

d

e

f

g

a

b

c

d

e

f

g

a. Deletion b. Duplication c. Inversion d. Translocation



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Changes in chromosome number

Nondisjunction occurs when both members of ahomologous pair go into the same daughter cellduring meiosis I or when sister chromatid failsto separate in meiosis II.

Results of nondisjunction: Monosomy: cell has only 1 copy of a chromosome

e.g., Turner syndrome (only one X chromosome)

Trisomy: cell has 3 copies of a chromosomee.g., Down syndrome (3 copies of chromosome 21)


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Aneuploidy

Individuals have one extra or less

chromosome

(2n + 1 or 2n - 1)

Major cause of human reproductive

failure

Most human miscarriages are

aneuploids


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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


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Nondisjunction

n+ 1

n+ 1

n- 1

n- 1chromosome

alignments at

metaphase Inondisjunction

at anaphase I

alignments at

metaphase II anaphase II

Figure 12.17Page 208


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Down Syndrome

Trisomy of chromosome 21

Mental impairment and a variety of

additional defects

Can be detected before birth

Risk of Down syndrome increasesdramatically in mothers over age 35



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Changes in sex chromosome number

Turner syndrome (X) short stature, broad shouldered with folds ofskin on the neck, underdeveloped sex organs, no breasts

Klinefelter syndrome (XXY) underdeveloped sex organs, breastdevelopment, large hands and long arms and legs

Poly-X female (XXX, XXXX) XXX tends to be tall and thin but not usually retarded

XXXX are severely retarded

Jacobs syndrome (XYY) tall, persistent acne, speech and reading

problems



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Changes in sex chromosome number


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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


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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


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XYY Condition

Taller than average males

Most otherwise phenotypically normal

Some mentally impaired

Once thought to be predisposed to

criminal behavior, but studies nowdiscredit


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Phenotypic Treatments

Symptoms of many genetic disorders

can be minimized or suppressed by

Dietary controls

Adjustments to environmental conditions

Surgery or hormonal treatments


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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


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Prenatal Diagnosis

Amniocentesis

Chorionic villus sampling

Fetoscopy

All methods have some risks


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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

14 chromosome and human genetics[revised]

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