Announcements

Discussion sections start next week. You will take a short pre-concept test-bring a pencil (it will not influence your grade in the course).

First Faculty Fellows Dining with Students lunch next Tuesday, Sept. 10, Noon, Jester City Limits.

Many human traits follow Mendelian patterns of inheritance

Humans are not good subjects for genetic research:
Generation time is too long Parents produce relatively few offspring Breeding experiments are unacceptable

However, basic Mendelian genetics endures as the foundation of human genetics.

Pedigree Analysis
A pedigree is a family tree that describes the interrelationships of parents and children across generations. Inheritance patterns of particular traits can be traced and described using pedigrees. Pedigrees can also be used to make predictions about future offspring.

Key
Male Female Affected male

Affected female
1st generation

Mating

Offspring

1st generation 2nd generation

Ff

Ff

ff

Ff

Ww

ww

ww

Ww

2nd generation FF or Ff ff ff Ff Ff

ff

Ww ww ww Ww 3rd generation

Ww

ww

3rd generation ff FF or Ff

WW or Ww
Widows peak

ww

No widows peak

Attached earlobe

Free earlobe

(a) Is a widows peak a dominant or recessive trait?

b) Is an attached earlobe a dominant or recessive trait?

Recessively Inherited Disorders

Many genetic disorders are inherited in a recessive manner. These range from relatively mild to lifethreatening.

The Behavior of Recessive Alleles

Recessively inherited disorders show up only in individuals homozygous for the allele. Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal; most individuals with recessive disorders are born to carrier parents. Albinism is a recessive condition characterized by a lack of pigmentation in skin and hair.

Parents Normal Aa Sperm A a Aa Normal (carrier) aa Albino Normal Aa

Eggs
A AA Normal Aa Normal (carrier)

 If a recessive allele that causes a disease is rare, then the chance of two carriers meeting and mating is low. However, matings between close relatives increase the chance of mating between two carriers of the same rare allele. Most societies and cultures have laws or taboos against marriages between close relatives.

Cystic Fibrosis
Cystic fibrosis is the most common lethal genetic disease in the United States, striking one out of every 2,500 people of European descent. The cystic fibrosis allele results in defective or absent chloride transport channels in plasma membranes leading to a buildup of chloride ions outside the cell. Symptoms include mucus buildup in some internal organs and abnormal absorption of nutrients in the small intestine.

Sickle-Cell Disease: A Genetic Disorder with Evolutionary Implications

Sickle-cell disease affects one out of 400 African-Americans. The disease is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells. In homozygous individuals, all hemoglobin is abnormal (sickle-cell). Symptoms include physical weakness, pain, organ damage, and even paralysis.

Fig. 14-UN1

Heterozygotes (said to have sickle-cell trait) are usually healthy but may suffer some symptoms. About one out of ten African Americans has sickle cell trait, an unusually high frequency of an allele with detrimental effects in homozygotes. Heterozygotes are less susceptible to the malaria parasite, so there is an obvious advantage to being heterozygous in some environments. This is the reason that the allele remains in the population.

Dominantly Inherited Disorders

Some human disorders are caused by dominant alleles. Dominant alleles that cause a lethal disease are rare and arise by mutation. Achondroplasia is a form of dwarfism caused by a rare dominant allele.

Parents Dwarf Dd Sperm D Eggs d Dd Dwarf Dd Dwarf dd Normal Normal dd

dd Normal

Huntingtons Disease: A Late-Onset Lethal Disease

The timing of onset of a disease significantly affects its inheritance. Huntingtons disease is a degenerative disease of the nervous system. The disease has no obvious phenotypic effects until the individual is about 35 to 40 years of age. Once the deterioration of the nervous system begins the condition is irreversible and fatal.

Multifactorial Disorders
Many diseases, such as heart disease, diabetes, alcoholism, mental illnesses, and cancer have both genetic and environmental components. Little is understood about the genetic contribution to most multifactorial diseases.

Genetic Testing and Counseling

Genetic counselors can provide information to prospective parents concerned about a family history for a specific disease. Using family histories, genetic counselors help couples determine the odds that their children will have genetic disorders. Probabilities are predicted on the most accurate information at the time; predicted probabilities may change as new information is available. For a growing number of diseases, tests are available that identify carriers and help define the odds more accurately.

Locating Genes Along Chromosomes

Mendels hereditary factors were genes. Today we can show that genes are located on chromosomes. The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene.

Mendelian inheritance has its physical basis in the behavior of chromosomes

Mitosis and meiosis were first described in the late 1800s. The chromosome theory of inheritance states: Mendelian genes have specific loci (positions) on chromosomes. Chromosomes undergo segregation and independent assortment. The behavior of chromosomes during meiosis can account for Mendels laws of segregation and independent assortment.

P Generation
Y Y R R

Yellow-round seeds (YYRR) y Meiosis Fertilization Gametes R Y y r ry r

Green-wrinkled seeds (yyrr)

All F1 plants produce yellow-round seeds (YyRr).

F1 Generation

R y r Y Meiosis

R r Y

LAW OF SEGREGATION The two alleles for each gene separate during gamete formation.

R
Y

r
Metaphase I y

LAW OF INDEPENDENT ASSORTMENT Alleles of genes on nonhomologous chromosomes assort independently during gamete formation. 1

1 R r Anaphase I Y R 2 Y Y R
1/ 4YR

r Y r

y r Metaphase II Y

y R 2 y

y y r
1/ 4

Gametes

Y R

y r yr

Y r
1/ 4

Y r Yr R

y R
1/ 4

yR

F2 Generation
3 Fertilization recombines the R and r alleles at random.

An F1 F1 cross-fertilization 9 : 3 : 3 : 1

Fertilization results in the 9:3:3:1 phenotypic ratio in the F2 generation.

Morgans Experimental Evidence: Scientific Inquiry

The first solid evidence associating a specific gene with a specific chromosome came from Thomas Hunt Morgan (18661945), an American embryologist. Morgan, in a series of experiments starting in about 1910 with fruit flies (Drosophila melanogaster), provided convincing evidence that chromosomes are the location of Mendels heritable factors.

Morgans Choice of Experimental Organism

Several characteristics make fruit flies a convenient organism for genetic studies: They produce many offspring. A generation can be bred every two weeks. They have only four pairs of chromosomes.

 Morgan noted wild type, or normal, phenotypes that were common in the fly populations. Traits alternative to the wild type are called mutant phenotypes.

Correlating Behavior of a Genes Alleles with Behavior of a Chromosome Pair

In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type): The F1 generation all had red eyes. The F2 generation showed the 3:1 red:white eye ratio, but only males had white eyes. Morgan determined that the white-eyed mutant allele must be located on the X chromosome. Morgans finding supported the chromosome theory of inheritance.

EXPERIMENT P Generation F1 Generation RESULTS F2 Generation

Figure 15.4

All offspring had red eyes.

CONCLUSION P Generation
X X w w X Y w

Eggs F1 Generation

Sperm
w
w

Eggs F2 Generation
w

Sperm
w w w

w w

Sex-linked genes exhibit unique patterns of inheritance

In humans and some other animals, there is a chromosomal basis of sex determination.

X Y

The Chromosomal Basis of Sex

In humans and other mammals, there are two varieties of sex chromosomes: a larger X chromosome and a smaller Y chromosome. Only the ends of the Y chromosome have regions that are homologous with corresponding regions of the X chromosome. The SRY gene on the Y chromosome codes for a protein that directs the development of male anatomical features.

 Females are XX, and males are XY. Each ovum contains an X chromosome, while a sperm may contain either an X or a Y chromosome. Other animals have different methods of sex determination.

Figure 15.6

44 XY

Parents

44 XX

22 22 X or Y

22 X

Sperm
44 XX

Egg or
44 XY

(a) The X-Y systemZygotes (offspring)

22 XX 22 X

(b) The X-0 system

76 ZW

76 ZZ

(c) The Z-W system

32 (Diploid) 16 (Haploid)

(d) The haplo-diploid system

Inheritance of X-Linked Genes

A gene that is located on either sex chromosome is called a sex-linked gene. Genes on the Y chromosome are called Ylinked genes; there are few of these. Genes on the X chromosome are called Xlinked genes. X chromosomes have genes for many characters unrelated to sex, whereas the Y chromosome mainly encodes genes related to sex determination.

 X-linked genes follow specific patterns of inheritance. For a recessive X-linked trait to be expressed:
A female needs two copies of the allele (homozygous). A male needs only one copy of the allele (hemizygous).

Therefore, X-linked recessive disorders are much more common in males than in females.

XNXN

XnY

XNXn

XNY

XNXn

XnY

Sperm Xn Eggs XN XN (a)

Sperm XN Eggs XN Xn (b)

Sperm Xn Eggs XN Xn (c)

XNXn XNY XNXn XNY

XNXN XNY

XNXn XNY

XNXn XnY

XnXn XnY

 Some disorders caused by recessive alleles on the X chromosome in humans: Color blindness (mostly X-linked) Duchenne muscular dystrophy Hemophilia

X Inactivation in Female Mammals

In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development. The inactive X condenses into a Barr body. If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character.

Figure 15.8

X chromosomes

Early embryo:

Allele for orange fur Allele for black fur

Two cell populations in adult cat: Active X

Cell division and X chromosome inactivation

Inactive X
Black fur Orange fur

Active X

Linked Genes
Each chromosome has hundreds or thousands of genes (except the Y chromosome). Genes located on the same chromosome that tend to be inherited together are called linked genes. This is because they are located near each other on the same chromosome.

How Linkage Affects Inheritance

Morgan did other experiments with fruit flies to see how linkage affects inheritance of two characters. Morgan crossed flies that differed in traits of body color and wing size.

EXPERIMENT

P Generation (homozygous)
Wild type (gray body, normal wings) b b vg vg

Figure 15.9-1

Double mutant (black body, vestigial wings) b b vg vg

EXPERIMENT

P Generation (homozygous)
Wild type (gray body, normal wings) b b vg vg F1 dihybrid (wild type) b b vg vg

Figure 15.9-2

Double mutant (black body, vestigial wings) b b vg vg TESTCROSS Double mutant

b b vg vg

EXPERIMENT

P Generation (homozygous)
Wild type (gray body, normal wings) b b vg vg F1 dihybrid (wild type) b b vg vg Testcross offspring

Figure 15.9-4

Double mutant (black body, vestigial wings) b b vg vg TESTCROSS Double mutant

b b vg vg Eggs b vg

b vg

b vg Grayvestigial

b vg

Wild type Black(gray-normal) vestigial

b vg

Blacknormal

Sperm

PREDICTED RATIOS

b b vg vg 1 1 : : :

b b vg vg 1 1 944 : : :

b b vg vg 1 0 206

b b vg vg

If genes are located on different chromosomes: If genes are located on the same chromosome and parental alleles are always inherited together:

:
: :

1 0 185

RESULTS

965

 Morgan found that body color and wing size are usually inherited together in specific combinations (parental phenotypes). He noted that these genes do not assort independently, and reasoned that they were on the same chromosome. However, nonparental phenotypes were also produced. Understanding this result involves exploring genetic recombination, the production of offspring with combinations of traits differing from either parent. And thus also relate to the chromosomal basis of recombination.

Recombination of Linked Genes: Crossing Over

Morgan discovered that genes can be linked, but the linkage was incomplete, because some recombinant phenotypes were observed. He proposed that some process must occasionally break the physical connection between genes on the same chromosome. That mechanism was the crossing over of homologous chromosomes.

Testcross parents

Gray body, normal wings (F1 dihybrid) b vg

Black body, vestigial wings (double mutant) b vg b vg Replication of chromosomes

b vg
Replication of chromosomes b vg

b vg b vg b vg b vg

b vg b vg
Meiosis I b vg

b vg b vg Meiosis I and II

b vg Meiosis II
b vg Recombinant chromosomes bvg b vg b vg b vg

Eggs

Testcross offspring

965 Wild type (gray-normal) b vg b vg

944 Blackvestigial

206 Grayvestigial b vg b vg

185 Blacknormal b vg b vg

b vg

b vg
b vg

Sperm

Parental-type offspring Recombination frequency

Recombinant offspring

391 recombinants 100 17% 2,300 total offspring

Mapping the Distance Between Genes Using Recombination Data

Alfred Sturtevant, one of Morgans students, constructed a genetic map, an ordered list of the genetic loci along a particular chromosome. Sturtevant predicted that the farther apart two genes are, the higher the probability that a crossover will occur between them and therefore the higher the recombination frequency.

Linkage maps
A linkage map is a genetic map of a chromosome based on recombination frequencies. Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency. Map units indicate relative distance and order, not precise locations of genes.

RESULTS Recombination frequencies 9% Chromosome 17% 9.5%

cn

vg

 Genes that are far apart on the same chromosome can have a recombination frequency near 50%. Such genes are physically linked, but genetically unlinked, and behave as if found on different chromosomes.

 Sturtevant used recombination frequencies to make linkage maps of fruit fly genes. Using methods like chromosomal banding, geneticists can develop cytogenetic maps of chromosomes. Cytogenetic maps indicate the positions of genes with respect to chromosomal features.

Mutant phenotypes Short aristae Black body Cinnabar Vestigial eyes wings Brown eyes

48.5 57.5

67.0

104.5

Long aristae (appendages on head)

Gray body

Red eyes

Normal wings

Red eyes

Wild-type phenotypes

Changes in chromosome number or structure cause some genetic disorders

Large-scale chromosomal alterations in humans and other mammals often lead to spontaneous abortions (miscarriages) or cause a variety of developmental disorders. Plants tolerate such genetic changes better than animals do.

Abnormal Chromosome Number

In nondisjunction, pairs of homologous chromosomes do not separate normally during meiosis. As a result, one gamete receives two of the same type of chromosome, and another gamete receives no copy.

Meiosis I

Nondisjunction

Meiosis I

Nondisjunction Meiosis II

Nondisjunction

Meiosis I

Nondisjunction Meiosis II

Nondisjunction Gametes

n 1 n 1 n 1 n 1
(a) Nondisjunction of homologous chromosomes in meiosis I

n 1 n 1

Number of chromosomes (b) Nondisjunction of sister chromatids in meiosis II

 Aneuploidy results from the fertilization of gametes in which nondisjunction occurred. Offspring with this condition have an abnormal number of a particular chromosome. A monosomic zygote has only one copy of a particular chromosome. A trisomic zygote has three copies of a particular chromosome.

 Polyploidy is a condition in which an organism has more than two complete sets of chromosomes:
Triploidy (3n) is three sets of chromosomes Tetraploidy (4n) is four sets of chromosomes

Polyploidy is common in plants, but not animals. Polyploids are more normal in appearance than aneuploids.

Alterations of Chromosome Structure

Breakage of a chromosome can lead to four types of changes in chromosome structure:
Deletion removes a chromosomal segment Duplication repeats a segment Inversion reverses orientation of a segment within a chromosome Translocation moves a segment from one chromosome to another

(a) Deletion
A B C D E F G H

A deletion removes a chromosomal segment.

A B C E F G H

(b) Duplication
A B C D E F G H

A duplication repeats a segment.

A B C B C D E F G H

(c) Inversion
A B C D E F G H

An inversion reverses a segment within a chromosome.

A D C B E F G H

(d) Translocation
A B C D E F G H M N O P Q R

A translocation moves a segment from one chromosome to a nonhomologous chromosome.

M N O C
D E F G H A B P Q R

Human Disorders Due to Chromosomal Alterations

Alterations of chromosome number and structure are associated with some serious disorders. Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond. These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy.

Down Syndrome (Trisomy 21)

Down syndrome is an aneuploid condition that results from three copies of chromosome 21. It affects about one out of every 700 children born in the United States. The frequency of Down syndrome increases with the age of the mother, a correlation that has not been explained.

Aneuploidy of Sex Chromosomes

Nondisjunction of sex chromosomes produces a variety of aneuploid conditions. Klinefelter syndrome is the result of an extra chromosome in a male, producing XXY individuals. Monosomy X, called Turner syndrome, produces X0 females, who are sterile; it is the only known viable monosomy in humans.

There are additional exceptions to standard Mendelian inheritance

One exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleus. In both cases, the sex of the parent contributing an allele is a factor in the pattern of inheritance.

Genomic Imprinting
For a few mammalian traits, the phenotype depends on which parent passed along the alleles for those traits. Such variation in phenotype is called genomic imprinting. Genomic imprinting involves the silencing of certain genes that are stamped with an imprint during gamete production.

Paternal chromosome Maternal chromosome (a) Homozygote

Normal Igf2 allele is expressed.

Normal Igf2 allele is not expressed.

Normal-sized mouse (wild type)

Mutant Igf2 allele inherited from mother

Mutant Igf2 allele inherited from father

Normal-sized mouse (wild type) Normal Igf2 allele is expressed.

Dwarf mouse (mutant) Mutant Igf2 allele is expressed.

Mutant Igf2 allele is not expressed.

Normal Igf2 allele is not expressed.

(b) Heterozygotes

 It appears that imprinting is the result of the methylation (addition of CH3) of cysteine nucleotides. Genomic imprinting is thought to affect only a small fraction of mammalian genes. Most imprinted genes are critical for embryonic development.

Inheritance of Organelle Genes

Extranuclear genes (or cytoplasmic genes) are found in organelles in the cytoplasm. Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules. Extranuclear genes are inherited maternally because the zygotes cytoplasm comes from the egg. The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant.

 Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems:
For example, mitochondrial myopathy and Lebers hereditary optic neuropathy

For next lecture

If you want more practice problems for genetic crosses, see the problems at the end of the chapter (or use the text study guide or access the online Mastering Biology with new texts). Read Chap. 22 and answer: - What exactly is natural selection? - What is adaptation? - How are the sources of genetic variation and principles of inheritance we already discussed essential to the process of evolution?