Chromosomes and Human Genetics

Starr/Taggart’s Biology:

The Unity and Diversity of Life, 9e

Chapter 12Notes edited by:R. LeBlanc, MS

(Revised: 1/2012)

1 2 3 4 5

6 7 8 9 10 11 12

13 14 15 16 17 18

19 20 21 22 X Y

•What happens to cell growth and division if gene(s) malfunction?

•Orderly cell growth and division are disrupted.

•What is the Philadelphia Chromosome?

•Chromosome #9; the 1st abnormal chromosome responsible for cancer.

•What happen to chromosome #9?

•Reciprocal translocation between #9 & #22 causing leukemia, a type of cancer.

•How does this effect genes on #9?

•The gene at the end of #9 is altered by the added gene from #22 causing an abnormal protein (uncontrolled division of white blood cells).

•What is leukemia? (Acute or chronic)

•Abnormal stem cells (Leukemias) over-produce white blood cells and push-out RBC’s and platelets.

•What are the function of stem cells?

•Cells that are unspecialized and others become specialized cells like RBC’s and platelets.

•What are white blood cells and what are their function? Platelets?

•Part of the bodies defense system.

•Used to help blood clotting.

Spectral Karyotyping

Key Concepts:

Each gene has its own position in sequence on a chromosome

Crossing over allows alleles in sequence to swap places

Allele recombination contributes to variations in phenotypes

The structure of chromosomes may change

Changes in chromosome structure can give rise to genetic abnormalities or disorders

Genes and Their Location

Genes are units of information about heritable traits

Each gene has its own location--a gene locus--on a particular chromosome

Alleles are different molecular forms of a gene Wild-type is most common form of allele.

Any less common form is mutant allele

•How many human genes are there?

•Of the nearly 24,000 human genes found in human DNA, more than 4,000 have been

patented by private firms and universities, a new study finds.

Types of Chromosomes

Autosomes Same in both sexes Human somatic cells have 22 pairs of

autosomesSex Chromosomes

Chromosomes that determine an individual’s sex (23rd pair)

Humans have 1 pair of sex chromosomes.

Karyotype Analysis (analyze the physical appearance 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)

Obtain a sample of cells; ex. Red blood

Stimulate mitosis with chemical & incubate. Add COLCHICINE to arrest mitosis at metaphase. Centrifuge machine

Draw off medium, add saline solution, and then a fixative.

Stain cellsTake picture of chromosomes; cut and arrange.

Human Karyotyping of somatic cells with 22 pairs of autosomes and 1 pair of sex chromosomes.

Fig. 12.4, p. 196

X

X Y

X

XX

XY

XX

XY

X X

Y

X

x

x

eggs sperm

diploidgerm cellsin female

diploidgerm cellsin male

Meiosis, gameteformation in bothfemale and male:

sex chromosomecombinations

possible in newindividual

Fertilization:

XY XX

Sex Determination

in Humans

Characteristics of the Y Chromosome

Y Chromosome The Y chromosome spans about 50

million base pairs (1.5 – 2% of total DNA).

The Y chromosome likely contains between 70 and 300 genes.

Involved in male sexual determination and development.

9 "disease genes" found on chromosome Y

Characteristics of the X Chromosome

The X chromosome spans about 155 million base pairs (about 5 percent of the total DNA in cells)

The X chromosome likely contains between 900 and 1,200 genes.

304 "disease genes" are found on chromosome X

Human Embryo and Sex Organ Development

XY Embryo 8 Weeks old

Gene on Y chromosome governs development of

testes (SRY: Sex-

determining Region on the Y Chromosome).

umbilical cord (lifeline between the embryo and the mother’s tissues)

amnion (a protective, fluid-filled sac surrounding and cushioning the embryo)

homozygous dominant female recessive male

Gametes:

XX X Y

XX X Y

Gametes:All F1 offspring have red eyes

x

x

1/4

1/4

1/4

1/4

1/2

1/2 1/2

1/2

F2

generation:

1. 1900’s Thomas Morgan

2. Link between sex determination & some non-sexual traits. (ex. Hemophilia; more in males)

3. White eyed flies appeared genetic mutations.

4. Recessive sex-linked trait or X-Linked)

-Why were there no white eyed flies in the 1st generation?

-Using a punnett square show the cross of the 2 parents & ratio of F1 offspring.

-Ratio of F2 offspring?

X-Linked Genes as Clues to Inheritance Patterns.

Comparing X-Linked and Sex-Influenced Traits

A CB

a cb

a CB

A CB

A cb

a cb

A CB

a cb

a cb

A CBCrossing Over and Recombination• One pair of homologous chromosomes in a duplicated state (each has 2 sister chromatids)

• 1 Blue & 1 Purple each with 3 different genes

• During prophase of meiosis 2 non-sister chromatids exchange segments.

• This represents 1 crossover event.

• This is the outcome of the crossover.

•Genetic recombination between non-sister chromatids.

Fig. 12.8, p. 199

normal chromosome 9

abnormal chromosome 9 (part ofanother chromosome attached to it

crossing over

recombinant chromosomes

Wx c

Wx c

wx C

Wx c

wx C

wx C

wx C

wx c

Wx c

Wx C

Chromosomes that can be distinguished physically with a special feature are called cytological markers.

C = colored seeds; c = colorless seeds

Wx = 2 forms of starch; wx = 1 form of starch.

During meiosis crossing over sometimes occurs.

Notice that the mutant chromosome is now associated with c.

Creighton & McClintock’s Experiment

An abnormal event caused a piece of a different chromosome to become attached.

Recombination Patterns and Chromosome Mapping

Experimental crosses with Drosophila (fruit flies)

Crossing over disrupts linkage groups (not rare)

Linkage: tendency of genes located on the same chromosome to be transmitted together in heritance.

Proved: Certain alleles tend to remain together during meiosis more often than others because they are positioned closer together on the same chromosome.

Linkage Mapping

Drosophila melonogaster Chromosomes

Probability that crossing over will disrupt linkage genes is proportional to the distance that separates the 2 loci.

1 Map Unit = 1% frequency of a crossover

What is the percent frequency What is the percent frequency between complete wings & long between complete wings & long wings?wings?

36.1 – 20 = 16.1% (chance of a recombination)

X Chromosome

A B C D

Suppose genes A and B are twice as far apart as two other genes, C and D. What would be the probability that genes A and B would cross over as compared to genes C and D?

The probability that crossover will disrupt their linkage is Proportional to the distance that separates the 2 loci; So…

AB are TWICE as likely to be disrupted by a crossover vs CD which are HALF as likely to.

Probability of a Crossover

Human Genetic Analysis

Pedigrees Genetic

corrections

Polydactyly

Regarding Human Genetic Disorders

Genetic abnormality (a rare uncommon version of a trait, Polydactyly; not life threatening)

Genetic disorder (inherited condition that sooner or later will cause mild to severe medical conditions.

Genetic disease (When workable genes get altered in away that disrupts body functions)

Genetic Examples of Disorders and Abnormalities: Autosomal recessive/dominant inheritance

X-Linked dominant/recessive inheritance

Changes in chromosome number

Changes in chromosome structure

Disease: an illness caused by infectious, dietary, or environmental factors; not by inherited traits.

Genetic Disorder

Some Important Genetic Disorders

Patterns of Autosomal Inheritance

Autosomal Recessive Inheritance Galactosemia (homozygous recessive)

lacking enzyme to digest lactose

Tay-Sachs Jewish descent metabolic disorder

Gene #15 mutated; enzyme hexa produced (dissolves nerve and brain cells fatty acids)

Harmful quantities of fatty acid are deposited in the nerve cells of the brain.

Die by age 5

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report (get form online)report (get form online)

LACTOSE GALACTOSEGALACTOSE-1-PHOSOPHATE

GALACTOSE-1-PHOSOPHATE

enzyme 1 enzyme 2 enzyme 3

+glucose intermediate

in glycolysis

• 1 in 100,000 chance of getting this inheritance.

•Enzyme 3 is not produced, so high levels of galactose start to accumulate.

•Galactose can be detected in urine.

•Damages: eyes, liver, and brain

•Untreated = death

•Treatment: restrict dairy products.

GalactosemiaGalactosemia

Patterns of Autosomal Inheritance

Autosomal Dominant Inheritance Progeria (rapid aging)

Huntington disorderProgressive involuntary

movements

Deterioration of the nervous system

Can cause death

Usually noticeable after age 40 causing parents to pass this on without their knowledge

Fig. 12.16, p. 206

Progeria – Too Young to be Old

Patterns of X - Linked Inheritance

X-Linked Recessive Inheritance Hemophilia

1 in 7000 males

Genes do not code for clotting agent

Duchenne Muscular Dystrophy

X-Linked Dominant Inheritance Faulty Enamel

Fig. 12.15, p. 205

Fragile X Syndrome (X-Linked recessive disorder)

•Causes a mutant gene

•Within this gene a segment of DNA is repeated several times; What kind of mutation is this:

•known as Expansion mutation

•Can you find the Fragile Site????

Chromosome Aberrations

Inversion Translocation

The physical structure of chromosomes can change resulting in a genetic disorder or abnormality. These can occur spontaneously.

Philadelphia

Chromosome

Chromosome Aberrations

Deletion DuplicationTriggered by:

•Viral attacks

•Irradiation (ionization radiation)

•Chemical assaults or other environmental factors.

Note: happens for chromosomes that code for polypeptides of hemoglobin and is not harmful.

Changes in Chromosome Number

Aneuploidy - One extra or one less chromosome

Polyploidy - Three or more of each chromosome

Nondisjunction causes changes in chromosome number (failure to separate during meiosis or mitosis)

Changes in the Number of Autosomes

Down Syndrome - Trisomy 21

•1 in 1100 in North America

•Show mental retardation

•40% have heart defects

Changes in the Number of Sex Chromosomes

Turner Syndrome X0 One X chromosome; 1 out of 2500 to 10,000 newborn girls.

Non-disjunction in sperm accounts for 75% of cases.

98% abort early in pregnancy.

Klinefelter’s Syndrome XXY 1 out of 500-2000 newborns

Non-disjunction; 67% in moms and 33% in fathers

Most infertile

XYY Condition 1 out of 1000 males

Tall; mildly retarded; most phenotypically normal

Changes in Chromosome Structure

Categories of chromosome aberration

Deletion

Duplication

Inversion

Translocation