Science 300:31 April 2003

Chromosome number error (aneuploidy) rose from 1-2% to 40% in mouse eggs!

Reason- bisphenol A (BPA), a component of plastic..

….. results in meiosis errors in mouse eggs normal

BPA treated

Meiosis

Environment-induced disruptions in meiosis

Chromosomes andHuman Genetics

Chapter 11

Chromosomes and CancerGenes on chromosomes drive ___________

__________ is uncontrolled cell division

Philadelphia Chromosome

•First abnormal chromosome to be associated with a cancer •Associated with a chronic ________

•Overproduction of white blood cells•Due to _____________________

Genes • Units of information about _______________

• Each has a particular __________

– Location on a _______________

•_______________ are identical in length, size, shape, and gene sequence

A CB

a cb

a cb

A CB

A CBA CB

a cba cb

a cba cb

A CBA CB

•Different __________ forms of a gene•Arise through _____________

Alleles

Fig. 11.4, p. 173

_______________- display of chromosomes

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)

Blood sample

1000X magnification

Sex Chromosomes• Discovered in late ______

• Mammals, fruit flies

– XX is _______, XY is _________

• In other groups XX is male, XY female

XX

XY

XX

XY

X X

Y

X XX

XY

XX

XY

XX

XY

XX

XY

X X

YY

XX

sex chromosome combinations possible in new individual

Y

X

YY

XX

sperm

X

X

X

X

eggs

Female germ cell Male germ cellSex determination

The Y Chromosome

• < ____ genes

• Includes ____ gene- dictates ______

phenotype

• > ______ genes• Most genes - _______ traits• Genes expressed in both males and females

The X Chromosome

Effect of YChromosome

10 weeks

Y present

Y absent

7 weeks

birth approaching

appearance of structuresthat will give rise toexternal genitalia

appearance of “uncommitted” duct system

of embryo at 7 weeks

Y present

Yabsent

testis

ovary

testes ovaries

• Thomas Hunt Morgan - first to associate a specific gene with a specific chromosome in the early 20th century.

• Morgan’s model-Drosophila melanogaster, a fruit fly - have three pairs of __________ and a pair of _____________ chromosomes (XX in females, XY in males).

Normal is called “_________”Red eyes White eyes

Non-normal is called “______”

• Morgan’s experiments-

Red eye X White eye

F1

3:1 Red:white

But- all __________were white, all females red

All Red eye

F2

Morgan concluded that a fly’s eye color was linked to the _ _____________ ___.

= _ _____ _

= _______ _

Know these symbols

Conclude- classic _ ________ _ genetics

Fig. 15.3

Chromosome- 1.5 x 108 base pairs containing about ______ genes

• Genes located on the same chromosome,___ ______ _______, tend to be inherited together because the chromosome is passed along as a unit.

Linked genes tend to be inherited together because they are located on the same chromosome

0.4% of a chromosome, containing 10 genes

15.3

15.215.1

14

13.3

13.11211

11.111.2

12

13.113.213.3

14

15

21

2223.1

23.3

31.131.231.3

3233.133.334

35.135.3

35.2

33.2

23.2

13.2

•Results of crosses with linked genes deviate from those expected according to __ _____________________ __.

Linkage Groups• Genes on one type of chromosome

• Fruit flies

– __ homologous chromosomes

– __ linkage groups

-____________to the distance that separates genes

A B C D

Crossing over will disrupt linkage between

_________ more often than _________

Crossover Frequency

Frequencies can be used to construct a _______________

Incomplete Linkage

Parents:

F1 offspring

Unequal ratios of four types of gametes:

All AaCc

x

meiosis, gamete formation

AC acA

C AC

AC

ac

ac

Ac

aC

ac

Most gametes have parental genotypes

A smaller number have recombinant genotypes

Linkage Mapping in Humans

• Chart that shows _____________ connections among individuals

• Knowledge of probability and Mendelian patterns used to suggest basis of a trait

Called a “________”

I

II

III

IV

V

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.*Gene not expressed in this carrier.

*

malefemale

Pedigree for __________

Unusual number of toes or fingers

Genetic Disorders

Autosomal _________

•_________ conditions that

cause mild to severe medical

problems

Autosomal __________

•Trait typically appears in _______ generation•Most of these ________ from population. WHY?

•Many people are _________•Heterozygous parents-- child will have a _____ chance of being affected

1. Huntington Disorder• Causes involuntary movements, nervous system

deterioration, death

• Symptoms don’t usually show up until person is past age ___

• People often pass allele on before they know they have it

Autosomal dominant diseases

•In homozygous form usually leads to _______• Heterozygotes display a type of _________• Have short arms and legs relative to other body parts

2. Acondroplasia

X-Linked Recessive Inheritance• Males show disorder

_________ females• Son _______ inherit

disorder from his father

1. Color blindness- 2. _________, Blood-clotting disorder; 1/7,000 males 3. ________- Allele has repeated segments of DNA; causes mental retardation4. ____________________ - Appears to be dominant; spontaneous mutation; premature aging effect, early death

Examples

Usually due to ________________

n + 1

n + 1

n - 1

n - 1chromosome alignments at metaphase I

nondisjunction at anaphase I

alignments at metaphase II anaphase II

The wrong number of chromosomes is bad

• Nondisjunction results in too many or to few chromosomes termed ______________ .– some gametes receive two of the same type of

chromosome and another gamete receives no copy.– _______ cells - three copies of a particular chromosome

type and have _______ total chromosomes.– _________ cells - one copy of a particular chromosome

type and have 2n - 1 chromosomes.

• Normally results in embryonic death, but some survive

Organisms with more than two _______ _sets of chromosomes, have undergone _________, e.g. 3n or 4n (rare in ____________)

• Polyploids are more nearly normal in phenotype than ___________.

Other chromosome problems

• An inversion - a chromosomal

fragment ________ to the original chromosome but in the reverse orientation.

• In_ _______, a chromosomal fragment joins a _________ chromosome.

Fig. 15.13c & d

•Some translocations are ___________ others are not.

A ________- a chromosome fragment lacking a ________ is lost during cell division

A ___________- a fragment becomes attached as an extra segment to a sister chromatid

• Homozygous embryos with a large ________ normally die

• A deletion in the X chromosome is _______ in males

• A __ ________________ can alter phenotype because a gene’s expression is influenced by its location.

Results of chromosome errors

Example- Leukemia is due to a growth gene being placed next to an active region resulting in cancer

• Approx. _____ of human embryos are aneuploid and die early in development

Some are viable-• Chromosome 15 trisomy- die at birth• Chromsome 21 trisomy- ________ syndrome

• Down syndrome- trisomy 21.– One in 700 children born in the United States.– result from ___________________ during

gamete production

Fig. 15.14• correlates with the age of the mother.

Karyotype

Phenotype

Extra sex chromosomes are allowed

• _____________________ _an XXY male, occurs once in every 2000 live births.

– Male sex organs, but are_ ________.

– Feminine characteristics; normal intelligence.

• Males with an extra Y chromosome (XYY) tend to somewhat _______ than average.

• Trisomy X (XXX), which occurs once in every 2000 live births, produces _ ________ _ females.

• Monosomy X or _____________ (X0), which occurs once in every 5000 births, produces phenotypic, but

immature females. • XYY and XXYY- males often found in _________.

• In utero testing for genetic screening. 1. _____________ - beginning at the 14th to 16th week of

pregnancy to assess the presence of a specific disease.Fig. 14.17a

•Fetal cells extracted from amniotic fluid are cultured and __________.

• 2. _____________ ________(CVS)- performed as early as the eighth to tenth week of pregnancy.

– Extracts a sample of fetal tissue from the chrionic villi of the placenta are karyotyped.

Fig. 14.17b

• Other techniques- ____________________________

allow fetal health to be assessed visually in utero.– usually reserved for cases in which the risk of

a genetic disorder or other type of birth defect is relatively great.

• If fetal tests reveal a serious disorder, the parents face the difficult choice of terminating the pregnancy or preparing to care for a child with a genetic disorder.