Chapter 12

Advanced Genetics

Mutations

• Mutation: a change in __.– May involve :

• an entire __

• a specific __

– may take place in __ cell

• When a mutation takes place the DNA is changed which affects the production of __. This may affect metabolism, development, or result in a new phenotype.

• Germ cell mutation - occurs in the __ cells.– This does not affect that organism but may be passed on

to the __.

Mutations in reproductive cells

• If this cell takes part in __, the altered gene would become part of the genetic makeup of the offspring.

Mutations in reproductive cells result in:• A __ mutation - the embryo does not survive.

• A __ that does not work correctly.

• In some rare cases it may have a __ effect.

• __ mutations - mutations in body cells– Ex)

• This mutation would __ be passed on to offspring.

Mutations in body cells

Mutations in body cells result in:

• Impairing the __ of the cell.

• When that cell divides, the new cells also will have the same mutation.

• Affecting genes that control __.– Cells may grow and divide rapidly, producing __

• A) __: a change in a single base pair in DNA. – A single nitrogen base is __ by another

• This may have __ noticeable affect or it can change the entire structure of a __ because a change in a single amino acid can affect the shape of the protein.

Types of Mutations

The effects of point mutations

Normal

Point mutation

mRNA

Protein Stop

StopmRNA

Protein

Replace G with A

• This mutation would cause nearly every __ in the protein after the __ to be changed.

• B) __: mutation in which a single base is added or deleted from DNA.

– Results in every __ after either the added or deleted base to be different.

Frameshift mutations

mRNA

ProteinFrameshift mutation

Deletion of U

• C) __: Structural changes in chromosomes. – Occur during __

– can be either changes in the __ of a chromosome or a __ of an entire chromosome.

– Are more __ types of mutations.

– __ are passed on to the next generation because the zygote usually dies.

– In cases where the zygote lives and develops, the mature organism is often __.

• 1) Deletion- __.– It breaks off and all that information is now lost.

Deletion

A B C D E F G H A B C E F G H

Types of Chromosomal Alterations

• 2) Duplication (__)- When part of a chromatid breaks off and attaches to its sister chromatid.

• The result is a duplication of genes on the __ chromosome.

Insertion

A B C D E F G H A B C B C D E F G H

Chromosomal Alterations

• 3) Inversion- When part of a chromosome breaks off and __.

Inversion

A B C D E F G H A D C B E F G H

Chromosomal Alterations

• 4) Translocation- When part of one chromosome breaks off and is added to __.

AB E FDCBXAWC HGGE HD F

WXY Z Y Z

Translocation

Chromosomal Alterations

• How? – Errors in __ (mistake in base pairing)

– Errors in __

• 1) __ mutations: mutations that just seem to happen

Causes of Mutations

• 2) __: Any agent that can cause a change in the __ (mutation)

• These are environmental factors such as:– a) __: such as X rays cosmic rays, ultraviolet light, and

nuclear radiation.– The energy they contain can damage or break apart __.

Causes of Mutations

Causes of Mutations

– b) __ mutagens: include dioxins, asbestos, benzene, and formaldehyde.• Usually cause substitution mutations

– c) __

*__- Procedure used to identify mutagenic substances.

Repairing DNA

• __ proofread the DNA and replace incorrect nucleotides with correct nucleotides.

• However, the __ the exposure to a mutagen such as UV light, the __ likely is the chance that a mistake will not be corrected.

• Pedigree: a graphic representation of __ inheritance.

– Like a __.

• It is a diagram made up of a set of __ that identifies individuals affected by the trait being studied, and family relationships.

Pedigrees illustrate inheritancePedigrees illustrate inheritance

Pedigrees illustrate

inheritance

Pedigrees illustrate

inheritance

Male

Female

Affected male

Affected female

Mating

Parents

Siblings

Known heterozygotes

for recessive allele

Death

• In a pedigree, a __ represents a female; a __ represents a male.

Pedigrees illustrate inheritance

Pedigrees illustrate inheritance

Female Male

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• Highlighted circles and squares represent individuals showing the trait being studied.

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Pedigrees illustrate inheritance

Pedigrees illustrate inheritance

Pedigrees illustrate inheritance

Pedigrees illustrate inheritance

• Circles and squares that are not highlighted designate individuals that do not show the trait.

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• A half-shaded circle or square represents a __: a heterozygous individual.

Pedigrees illustrate inheritancePedigrees illustrate inheritance

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Pedigrees illustrate inheritancePedigrees illustrate inheritance• A horizontal line

connecting a circle and a square indicates that the individuals are parents (__ line), and a vertical line connects parents with their offspring (__ line).

Pedigrees illustrate inheritancePedigrees illustrate inheritance• Each horizontal

row of circles and squares in a pedigree designates a __, with the most recent generation shown at the bottom.

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Pedigrees illustrate inheritancePedigrees illustrate inheritance• The generations

are identified in sequence by __, and each individual is given an Arabic number.

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• 1) __: an examination of a persons genetic makeup.

– This may involve:

• A) Blood test - looks for the presence or absence of certain __

Detecting Genetic Disorders

• B) Karyotype- __.

– Procedure: remove __ from a cell

– stain and photograph chromosomes

– cut out each chromosome

– match it with its __

Detecting Genetic Disorders

• 1) __- uses high-frequency sound waves to produce an image of a fetus on a moniter

– image is called a __

• 2) Amniocentesis- __.– Use a needle and syringe to remove some amniotic fluid.

– Make a __ and analyze.

Detecting Genetic Disorders: In a fetus

• 3) Chorion villi sampling- analyze a sample of the chorion villi (tissue that grows between the __.)

– villi has the same __as the fetus.

• 4) __- a visual procedure for observing disorders in the fetus.

– Uses an instrument called an __

– can: observe fetus’ development, take skin and blood samples for analysis, do blood transfusions, and remove excess fluid from the brian.

Detecting Genetic Disorders: In a fetus

Simple Recessive HereditySimple Recessive Heredity• Most genetic disorders are caused by __ alleles.

1) Cystic fibrosis1) Cystic fibrosis

• Due to a defective __ in the cell membrane.

• Results in the formation and accumulation of thick __ in the lungs and digestive tract.

• Common among __. (1 in 28 carries the allele, 1 in 2500 inherits the disorder)

• Average lifespan: __ yrs.

2) Tay-Sachs disease2) Tay-Sachs disease

• Tay-Sachs (tay saks): a recessive disorder of the __.

• Results in the absence of an __ that normally breaks down a __ produced and stored in tissues of the central nervous system.

• Therefore, lipids accumulate in the cells.

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Typical Pedigree

for

Typical Pedigree

for

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• Phenylketonuria (fen ul kee tun YOO ree uh): (PKU) the absence of an __ that converts one amino acid, phenylalanine, to a different amino acid, tyrosine.

• Phenylalanine and its by-products accumulate in the body resulting in severe damage to the __.

• A PKU test is normally performed on all __ a few days after birth.

• Infants affected by PKU are given a diet that is low in __ until their __ are fully developed.

3) Phenylketonuria3) Phenylketonuria

• New Problem: If a female who is homozygous recessive for PKU becomes __, the high phenylalanine levels in her blood can damage her __ - the developing baby.

• This problem occurs even if the fetus is __ and would be phenotypically normal.

PhenylketonuriaPhenylketonuria

PhenylketonuriaPhenylketonuria

Phenylketonurics: Contains Phenylalanine

Simple Dominant HereditySimple Dominant Heredity

• A single dominant allele inherited from __ parent is all that is needed for a person to show the dominant trait.

Simple dominant traits:Simple dominant traits:• 1) __

• 2) widow’s __

• 3) hitchhiker’s thumb

• 4) almond shaped __

• 5) thick lips

• 6) presence of __ on the middle section of you fingers

Huntington’s diseaseHuntington’s disease• A __ genetic disorder

• Caused by a rare __ allele.

• Results in a breakdown of certain areas of the __.

• Symptoms: __ and irritability, eventually lose of __ control, uncontrollable physical __, severe mental illness, and eventually __.

Huntington’s diseaseHuntington’s disease

• __: a short section of __ that indicates the presence of an allele that codes for a trait.

– __of people with this marker have a chance of developing HD

– can test before they have __.

• Usually occurs between the ages of __– An individual may already have had children

before knowing whether he or she is affected.

Typical Pedigree of Huntington’s DiseaseTypical Pedigree of Huntington’s DiseaseI

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Question 1 What does

this pedigree tell you about those who show the recessive phenotype for the disease?

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The pedigree indicates that showing the recessive phenotype for the disease is __.

• Thomas Hunt __ (early 1900’s) – Began a series of breeding experiments with Drosophila

melanogaster (__) Why use fruit flies?• Easy to maintain in a laboratory

• have a generation time of only __ days

• produce __ of offspring from each mating

• have easily distinguishable __ characteristics

• have only __ chromosomes

Genetic PatternsGenetic Patterns

• He discovered that __ pair of chromosomes were different in males and females.

– In females: all pairs were __

– In males: the __ pair was different

• He called the large chromosome in the 4th pair the “__” chromosome and he called the short hooked one the “__” chromosome.

• The same applies to __.– Other organisms differ

Genetic PatternsGenetic Patterns

• In humans the __ number of chromosomes is 46, or 23 pairs.

• __: A chromosome that is not a sex chromosome. There are __ pairs of homologous autosomes in humans. They all look alike.

• __ chromosomes: Chromosomes that determine an individual’s sex. They are the __ pair in humans and they differ in males and females.

Sex determinationSex determination

Sex determinationSex determination• If you are __, your 23rd

pair of chromosomes are homologous, __.

• If you are __, your 23rd

pair of chromosomes __, look different.

X XFemale

YXMale

• Males: Produce two kinds of __, X and Y.

• Females: Produce only __ gametes.

• It is the __ gamete that determines the sex of the offspring.

Sex determinationSex determination

Sex determinationSex determination

XX Female

XY Male

X

X

X Y

XX Female

XY Male

XX Female

XY Male

• __ hypothesized that some traits were always associated with one __ or the other.

– Ex) Most fruit flies have __ eyes • crossed a white-eyed male with a red-eyed female

• F1 - all had red eyes

• His hypothesis: The allele for eye color in fruit flies must be carried on the __ chromosome.

• Next he crossed the F1 generation

• expected a __ratio. He got it BUT…..

• Noticed all white-eyed flies were __. (in this example)

Sex-linked inheritanceSex-linked inheritance

• Sex-linked traits: Traits controlled by genes located on the __.

• The alleles for sex-linked traits are written as __ of the X or Y chromosomes.

• The __ chromosome has no corresponding allele to one on the X chromosome and no __ is used. (Since X and Y are not homologous)

• Therefore, any __ allele on the X chromosome of a male will __ be masked by an allele on the Y chromosome.

Sex-linked inheritanceSex-linked inheritance

Females:

Males:1/2 red eyed

1/2 white eyed

all red eyed

White-eyed male (XrY)

Red-eyed female (XRXR)

F1 All red eyed

F2

Sex-linked inheritanceSex-linked inheritance

• Many human traits are determined by genes that are carried on the __; most of these genes are located on the __ chromosome. (Not the Y)

Sex-Linked Traits in Humans

• These traits are more common in __. WHY?– The __ chromosome does not carry a gene for these

traits so whatever allele is on the X chromosome is what trait will be expressed. (Dominant or recessive)

– Sons inherit these traits from their __ since that is who they are receiving the __ chromosome from.

• Females, who are XX, pass one of their X chromosomes to __ child.

Sex-Linked Traits in Humans

Male Female

Sperm Eggs

FemaleFemale MaleMale

Female Male

MaleMaleFemale Female

Eggs Sperm

• Caused by a __ allele

• These people can’t differentiate between red or green.

• __of males are color blind.

• Is __ in females.

Example: __color blindness

• Hemophilia A: The __ does not clot properly because it lacks a __ essential for clotting.

Example: Hemophilia

• __: about one in every 10 000 has hemophilia. __: only about one in 100 million inherits it.

– Females would need __ recessive alleles to inherit hemophilia.

– Males inherit it from their carrier __. (One allele will cause the disorder in males.)

• Polygenic inheritance: is the inheritance pattern of a trait that is controlled by __.

• Genes may be on the __ chromosome or on __ chromosomes. (Each gene may have two or more alleles.)

• All heterozygotes are __ in phenotype.– Phenotypes show a continuous range of variability.

– Ex) Plants: • aabbcc - 4cm tall

• AABBCC - 16cm tall

•

Polygenic inheritancePolygenic inheritance

• Examples:– __

– __

– __

– __

Polygenic Inheritance in Humans

• The __ genes, the __ ranges of skin color.

• Scientists found that when light-skinned people mate with dark-skinned people, their offspring have __ skin colors.

__: A polygenic trait

• This graph shows the expected distribution of human skin color if controlled by one, three, or four genes.

Skin color: A polygenic trait

Number of Genes Involved in Skin Color

Observed distribution of skin color

Expected distribution- 1 gene

Expected distribution- 4 genes

Expected distribution- 3 genes

Range of skin color

Light Right

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Studying Human GeneticsStudying Human Genetics• Problem:

– May take __ years to produce 3 generations of humans.

– Each generation will produce only a __ individuals.

– Because of ethical __, scientists are prevented from using same procedures they would use on other organisms.

• Human inheritance patterns are very complicated. Their chromosomes contain atleast __ genes (7 times more than Drosopohila)

– SO……. How do scientists go about it?

Studying Human GeneticsStudying Human Genetics• 1) Population sampling: __

– use carefully formulated statistical rules to select members of a sample to ensure they get accurate results.

– Ex) Used to estimate the percentage of people in the U.S. who could __ the chemical phenylthiocarbamide (PTC)

– “Tasters” - detect a bitter taste to PTC (65% of pop.)

– “Nontasters” do not detect any taste (35% of pop.)

Studying Human GeneticsStudying Human Genetics• 2) __: Geneticists study __ twins to distinguish

between genetic and environmental influences on certain traits.

– Identical twins - have the same __ information. Differences may result from environmental influences (home life, education, etc…) Is more easily studied if raised by __ families.

• 3) __: Shows how traits have been passed down through the __.

Environmental InfluencesEnvironmental Influences• The genetic makeup of an organism only determines

the organism’s __.

• As the organism develops, many factors can influence how the __ is expressed, or even if it is expressed at all.

• Two influences are:– 1) __ environment

– 2) __ environment

• A)

• B)

• C)

• D)

• E)

Influence of external environmentInfluence of external environment

Influence of external environmentInfluence of external environment

• In arctic foxes __ has an effect on the expression of coat color.

• External influences can also be seen in leaves. Leaves can have different sizes, thicknesses, and shapes depending on the amount of __ they receive.

Influence of external environmentInfluence of external environment

Influence of internal environmentInfluence of internal environment• A) __-influenced trait:

trait that is influenced by the presence of male or female sex __. Males and females have different hormones therefore __ are expresses differently.

– Ex) __ pattern baldness• __ in males

• __ in females

• B) __ can also affect gene function.

• Both alleles are __ expressed in the heterozygous offspring.

__ in Humans

• Example: Sickle-cell disease (Sickle-cell anemia)

• A - dominant allele, produces normal __

• A` - codominant allele, produces abnormal hemoglobin. (affects ability to carry __)

• AA` - have both __ and __ hemoglobin

Sickle-cell disease

– The defective hemoglobin changes the shape of the __. • Normal red blood cells are __-shaped

• Abnormal red blood cells are shaped like a __, or half-moon.

• The change in shape occurs in the body’s narrow __ after the hemoglobin delivers oxygen to the cells.

Sickle-cell disease

Normal red blood cell

Sickle cell

Sickle-cell disease• Results in : 1) Impairing the flow of __ 2) Slows __

flow, 3) __ clots, 4) Tissue damage and __ 5) __, 6) __, 7) Eventually failure of vital __.

Normal red blood cell

Sickle cell

• Affects mainly __ population.– In U.S. __ of Black population carry the sickle-cell allele

– In Africa as many as __ carry it.

Sickle-cell disease

• Advantage to being a carrier:

• The parasite responsible for __ cannot survive in sickle cells, therefore, they are more likely to survive malaria.

• Cause by a __ allele. Huntington’s Disease (HD)

• Symptoms: Forgetfulness, irritability first. Eventually loss of muscle control, uncontrollable physical spasms, severe mental illness, eventually death.

• Problem: Carriers do not know they have the disease until after they’ve had __.

• __: a short section of __ that indicates the presence of an allele that codes for a trait.

– Ex) __of people with this marker develop HD

• __: when a replicated chromosome pair fails to separate during cell division.

Changes in Chromosome Numbers

• One daughter cell receives an __ chromosome and the other daughter cell __ a chromosome.

• Trisomoy: Cells that have an __ autosome (they have __ of a particular chromosome instead of two.)

– Results in __ chromosomes

Abnormal numbers of autosomes

• Monosomy: Cells that are __ an autosome. (they have __ of a particular chromosome instead of two.)

– Results in __ chromosomes

• Results from trisomy of chromosome __.

__ syndrome: Trisomy 21

• Individuals who have Down syndrome have at least some degree of __ retardation, folds of skin above the __, weak __, enlarged tongue, a rounder, fuller face, and are __ in height.

• The incidence of Down syndrome births is higher in older mothers, especially those over __.

• Down syndrome is the __ autosomal trisomy in which affected individuals __ to adulthood.

Down syndrome: Trisomy 21

• It occurs in about one in __ live births.

• Klinefelters Syndrome: – caused by __

– results in a __ of XXY

– is a __ with mental retardation, and low fertility

– occurs 1:1000 births

Abnormal numbers of sex chromosomes

• __ Syndrome: – caused by nondisjunction

– results in a __ of XO

– is a __ with immature physical development, sterility, and webbed neck.

– Occurs 1: 10,000 births

• Genome: __.

• Human __ Project (HGP): organized by scientists in the United States in __.

– It is an international effort to completely __ and sequence the approximately 35,000-40,000 __ on the 46 human chromosomes. (human genome)

Mapping and Sequencing the Human Genome

• In February of 2001, the HGP published its working draft of the __ base pairs of __ in most human cells.

Mapping and Sequencing the Human Genome

• Improved techniques for prenatal diagnosis of human __, use of __ therapy, and development of new methods of __ detection are areas currently being researched.

Applications of the Human Genome Project

• Linkage map (__): Shows the relative locations of __ on a chromosome.

– These genes are usually __ together

– Exception: __

Linkage maps

• These maps are made by studying the __data

• Example using Drosophila– wing shape/eye color: linked 90% of the time, crossed

over __ of the time.

– Wing shape/body color: linked 93% of the time, crossed over __ of the time.

– Eye color/ body color: linked 83% of the time, crossed over __ of the time.

Linkage maps

• This information is used to create a linkage map. (Atleast __ traits must be compared)

• __: A unit in chromosome mapping equal to a __ occurrence of crossing over.

Linkage maps

• Example: If wing shape and eye color cross over 10 % of the time then they are __ map units apart.