http://evolution.berkeley.edu

Biology ReviewGenetics

2

Much of the text material is from, “Essential Biology with Physiology” by Neil A. Campbell, Jane B. Reece, and Eric J.

Simon (2004 and 2008). I don’t claim authorship. Other sources are noted when they are used.

Note

3

Outline

• Patterns of inheritance• Beyond Mendel

4

Patterns of Inheritance

http://www.southwesternexposure.com

5

Gregor Mendel

http

://ke

ntsi

mm

ons.

uwin

nipe

g.ca

1822 - 1884

6

Gregor Mendel

• Gregor Mendel was first to analyze patterns of inheritance in a system-atic, scientific manner.

• During the 1860s, he deduced the fundamental principles of genetics by breeding garden peas in an abbey garden in Brunn, Austria, which is now part of the Czech Republic.

• He was strongly influenced by physics, mathematics, and chemistry in applying experimental techniques and mathematics to the study of pea plants and inheritance.

• Mendel’s work, along with that of his (unknown) contemporary, Charles Darwin, is a classic in science.

7

Inherited Characteristics

• Mendel postulated in a paper published in 1866 that parents pass on factors to their offspring that are responsible for inherited characteris-tics.

• He found that these factors retain their uniqueness from generation to generation—these factors are what we now call genes.

• Mendel’s work is a major foundation of modern biology and genetics, and provides the biological mechanism for natural selection postulated by Darwin.

Postulate = to make a claim; to assume or assert a truth.

8

Pea Plants

http

://up

load

.wik

imed

ia.o

rg

Pea pods

Pea flowers

http

://up

load

.wik

imed

ia.o

rg

9

Why Study Pea Plants?

• Mendel chose garden peas because they exist in readily distinguish-able varieties and are easy to grow.

• He could also strictly control the transfer of pollen for fertilization to produce offspring.

• The breeding cycle is short, so he could study many generations in a short period of time.

10

Fertilization

• Pea plants can self-fertilize when the pollen from the stamens settle on the stigma of the same flower.

• Mendel could assure self-fertilization by covering the flower with a bag so that no pollen grains from other pea plants could reach the stigma.

• He controlled cross-fertilization (crosses) by pollinating other pea plants using a small brush.

• Using these methods, the precise parentage of the offspring could be determined.

11

Pea Plant Characteristics

Dominant is to the left and recessive is to the right for each of the seven characteristics that Mendel studied.

http

://m

ac12

2.cu

.ac.

jp

Seed shape

Seed color

Flower color

Pod shape

Pod color

Flowerposition

Stemheighth

12

Monohybrid Cross

P generation (true-breeding varieties): purple flowers x white flowers

F1 generation: purple flowers x purple flowers

F2 generation: 3/4 purple flowers and 1/4 white flowers

Fertilization

Fertilization

13

Genotype and Phenotype

• Mendel’s experiment led to a conclusion that have been confirmed many times by biologists and geneticists:

• The physical traits of an organism are its phenotype, and its genetic makeup is its genotype.

An organism’s appearance does not always reveal its inherited traits, or genetic composition.

14

Mendel’s Hypothesis

1. Alternative forms of alleles, what we now call genes, determine phen-otype or inherited characteristics.

2. For each inherited characteristic, an organism has two alleles, one from each parent.

3. An egg and sperm each carries an allele for each inherited character-istic, which are paired during fertilization.

4. For each allele pair, the one that is fully expressed in the phenotype is the dominant allele, and the one that has no noticeable effect is the recessive allele.

Dominant alleles are represented by uppercase letters and recessive alleles by lowercase letters.

15

Punnett Square

PP

Pp Pp

pp

P P

pp

P

PP

Pp

p

PpP

p ppParent 1

Parent 2

Parent 1 Parent 2

PP—purple flowersPp—purple flowerspp—white flowers

Clockwise rotation by 45o

The Punnett square is a visual tool for showing all combinations

of alleles of an inherited characteristic.

Reginald C. Punnett (1875-1967)http://www.epidemiology.ch

16

Principle of Segregation

• Mendel found the same type of inheritance pattern occurred for all seven characteristics of peas that he studied.

• For a true-breeding variety, one parental trait disappears in the F1 generation and then reappears in one-fourth of the F2 generation.

• The underlying mechanism is known as Mendel’s principle of segre-gation.

17

Principle of Segregation (continued)

• The principle conveys that pairs of alleles segregate—or separate— during meiosis, and the fusion of gametes at fertilization creates allele pairs once again.

• Research over the past ~150 years has shown the principle applies to all sexually-reproducing organisms for non-linked genes (more about this later).

18

Homologous Chromosomes

• A pair of chromosomes, as we discussed in the lecture on reproduc-tion, is homologous—one is from the female parent and one is from the male parent.

• A homologous pair has the same alleles (such as for flower color) at the same locus, or location, on the chromosomes.

Locus = singular; loci = plural.

19

Homologous Chromosomes (continued)

Genes are shown as three banded colors on the chromosome fragments.

The letters for the three gene loci are arbitrary and are only used to convey the concepts.

P s C

P s c

Genotypes: PP ss Cc

Homozygousfor the

dominant allele

Homozygousfor the

recessive allele

Heterozygous

Homo- = sameHetero- = different

20

Principle of Independent Assortment

• What would result from a dihybrid cross, the mating of parents differing in seed shape and seed color?

• Mendel found the yield ratios in the F2 generation were the same as if seed shape and color were studied as separate monohybrid crosses.

• Mendel’s principle of independent assortment states that each pair of alleles segregates independently of other pairs of alleles during gamete formation.

• This is true for genes that are not linked, which Mendel fortunately hap-pened upon in his work with pea plants.

21

Testcross

• A testcross involves mating an organism of unknown genotype with a known, heterozygous organism (Pp).

• The unknown genotype is determined by observing the F2 yields and inferring the parentage.

• Mendel used the method to confirm if he had true-breeding varieties of pea plants.

• Testcrosses are still used by geneticists to determine unknown geno-types.

Observe

P ?

?pParent 1 Parent 2

Observe

Observe Observe

22

Can you create an example of a testcross?

23

Probability

Morgan Silver Dollar minted in 1895 (tails)http://z.about.com

• The segregation of allele pairs during gamete formation (meiosis) and the reforming of allele pairs during fertilization follow the rules of probability.

• The same rules apply to tossing a coin, rolling a die, and drawing playing cards.

• Just as in probability experiments, Mendel found that he needed to obtain large sample sizes of F1 and F2 offspring since random vari-ation exists.

24

Probability Visualized

Yields:PP = 1/4Pp = 1/4 + 1/4 = 1/2pp = 1/4

PP1/4

Pp1/4

Pp1/4

pp1/4

P P

pp

1/2

1/21/2

1/2

F2 genotypes

F1 genotypes

Pp—female

Egg (P or p)

Pp—male

Sperm (P or p)

Meiosis

(Random chance in fertilization)http://www.rpi.edu

25

Complex Genetic Problems

• The results for the rule of multiplication work out the same as for a Punnett square.

• The outcomes of trihybrid crosses involving three different charac-teristics can be calculated using probability rules.

• In comparison, it would be difficult to analyze a trihybrid cross using the Punnett tool.

• Complex genetic problems are typically solved by applying rules of probability to the principles of segregation and independent assort-ment.

26

Inheritance of Human Traits

• Mendel’s principles apply to the inheritance of a number of human traits including those we will discuss next.

• Each of these traits is the result of simple dominant-recessive inher-itance at one gene locus (position).

• The genetic basis of some human characteristics, such as eye color and hair color, are not as well understood since multiple gene loci are involved.

27

Dominant Phenotype

• Dominant refers to the expression of alleles in a homologous gene pair.

• Dominant does not imply that a phenotype is necessarily more com-mon than a recessive phenotype.

• For example, freckles are the result of a dominant allele but they are not common in the general population.

28

Handedness and Cerebral Specialization

Einstein’s brain, from the medical journal, The Lancethttp://www.answers.com

Right-handed—the left hemisphere contains the processing areas for verbal and mathematical abilities.

Left-handed—the right hemisphere often contains the areas for verbal

and math abilities.

Handedness is not the result of a single gene, and is not fully-

understood.

29

Family Pedigree

• Geneticists, for obvious reasons, are unable to control the matings of humans, unlike researchers working with pea plants or other or-ganisms.

• Instead, they analyze the results of matings in humans that already occurred.

30

Family Pedigree (continued)

• A geneticist collects as much information as possible about a family’s history for a phenotype.

• The information is assembled into a upside-down, tree structure known as a family pedigree.

• The geneticist uses the concepts of dominant and recessive alleles and the principle of segregation for analyzing family pedigree to determine if an inheritance pattern exists.

31

Case Study

• A classic study was the construction of family pedigrees for a rare type of deafness on Martha’s Vineyard, a once-remote island off the coast of Massachusetts.

• This form of deafness results from a homozygous recessive genotype (which we will call, dd).

• Family members with a heterozygous genotype (Dd) are not deaf, but they are carriers of the disorder.

• Members with a homozygous dominant genotype (DD) are neither deaf nor carriers.

32

Martha’s Vineyard

The isolation of Martha’s Vineyard help foster marriages between close relatives between about 1700 and 1900. The frequency of deafness was

high since there was little exchange of alleles with outsiders.

http

://m

a.w

ater

.usg

s.go

v

Martha’s Vineyard

http://www.mass.gov

33

Punnett Square

The appearance of deafness from generation-to-generation on Martha’s Vineyard can be solved using either a 2 x 2 Punnett square or the rule of

multiplication.

DD

Dd Dd

dd

D D

ddMother Father

Which offspring of two heterozygous parents (Dd) will be deaf and which will be carriers?

34

Family Pedigree for Deafness

http://www.myops.org

A sketch of a family pedigree showing inheritance of deafness.

Females are shown by circles and males by squares.Deafness is indicated by dark symbols representing an allele pattern of dd.

Hearing is indicated by light symbols representing an allele pattern of DD or Dd.

35

Inheritance Patterns

• The hereditary deafness observed on Martha’s Vineyard is one of over a thousand genetic disorders of dominant or recessive traits controlled by single genes.

• These disorders have simple inheritance patterns just like the traits Mendel studied in pea plants.

• The genes are all located on the autosomes—that is, chromosomes other than X and Y in the 23rd set.

36

Inbreeding

• Mating of close relatives—called inbreeding—can produce offspring who are homozygous for a harmful recessive trait because the allele is more likely to be encountered.

• Many societies have taboos and laws to forbid marriages between close relatives.

• The legal prohibitions may have first formed from observations that still-births and birth defects are more common when two parents are closely-related.

37

Inbreeding (continued)

• Some small and isolated groups of animals, such as cheetahs, show the detrimental effects of inbreeding, which could lead to their extinc-tion.

http

://lh

6.gg

pht.c

om

http

s://g

6n.w

ikis

pace

s.co

m

38

Likelihood of Genetic Disorders

• People who share recent common ancestors are more likely to carry the same alleles than unrelated people.

• Due to increased mobility in modern societies, it is relatively unlikely that two carriers of a rare and harmful allele will meet and have chil-dren.

39

Recessive Disorders

• Human genetic disorders are usually recessive, and they they can range in severity from relatively harmless to life-threatening.

• Most people afflicted with recessive disorders are born to parents who are heterozygous; that is, they are carriers but don’t have the disorder.

• As with the rare form of deafness on Martha’s Vineyard, the percent-age of affected offspring can be predicted by the matings of the two parents.

• Examples of single-gene recessive disorders include albinism, sickle-cell disease, Tay-Sachs, phenylketonuria, galactosemia, and cystic fibrosis.

40

Cystic Fibrosis

• Cystic fibrosis is the most common lethal genetic disorder in the United States.

• It affects about one in 1,800 European Americans, and is carried as a recessive allele by about one in 25 people.

• The disease affects about one in 17,000 African Americans, and about one in about 90,000 Asian Americans.

http

://im

ages

.cff.

org

41

Physical Effects

• A thick mucus is secreted by lungs, pancreas, and other body organs in cystic fibrosis.

• The mucus can interfere with breathing, digestion and liver function, and can make the person more vulnerable to pneumonia and other opportunistic bacterial infections.

• The lives of children afflicted with the disorder can often be extended with:- Special diets- Frequent pounding of the chest and back to clear the lungs- Antibiotics- Other treatments

42

Dominant Disorders

• Some human disorders are the result of dominant alleles—they are far less common than those resulting from recessive alleles.

• One reason for being less common is that dominant alleles also affect the carrier.

43

Dominant Disorders (continued)

• Lethal dominant alleles may kill the embryo, or the afflicted individual may not live long enough to reproduce.

• This is in contrast to recessive alleles passed from generation-to-generation by heterozygous carriers who do not exhibit the disorder.

• A few dominant disorders such as extra or webbed fingers and toes, are not lethal.

http

://ke

ckm

edic

ine.

adam

.com

44

Achondroplasia

• Achondroplasia is characterized by very short stature, with arms and legs that are too short for the torso.

• About one in 25,000 people have this disorder.• Only individuals with a single copy of the dominant allele (Aa) have the

disorder because the homozygous genotype (AA) results in the death of an embryo.

• A person with achondroplasia has a 50 percent chance (p = 0.50) of passing the dominant allele to his or her offspring that survive to birth.

• This pattern can be demonstrated using a Punnett square or the rule of multiplication.

45

Resources and Support

http://www.icongrouponline.com

TopLittle People of America

http://www.flickr.com

LeftConference gatheringhttp://www.ksginfo.org

46

Huntington’s Disease

• A lethal dominant allele can escape early detection if it does not result in death until later in life.

• Huntington’s disease, which causes progressive degeneration of the nervous system, is not apparent until middle age.

• Symptoms include uncontrolled movements, memory loss, impaired judgment, depression, and in later stages, an inability to swallow and speak.

• Death usually occurs 10 to 20 years after onset of the first symptoms.

47

Late Appearance of Symptoms

• By the time symptoms are evident, the afflicted individual may have had children—about half will have received the lethal dominant allele.

• A famous case involved the singer-songwriter, Woody Guthrie, who died from the disease in 1967, at the age of 55.

• His children, Nora and Arlo, were at risk for the disease although they now have passed that point in their lives.

http

://w

ww

.adl

itera

te.c

om

48

What are some basic differences between recessive and dominant disorders?

49

The last Russian Czar Nicholas, Alexandra, and Childrenhttp://img.dailymail.com.uk

Beyond Mendel

50

Snapdragons

http

://w

ww

.elli

otba

ker.c

om

51

Incomplete Dominance

• In Mendel’s pea plants, an F1 hybrid looked like one of the parents due to the dominant allele.

• In some organisms, F1 hybrids can express an intermediate pheno-type between those of the two parents.

• For example, when red and white snapdragons are crossed, all of the F1 hybrids have pink flowers—not red flowers or white flowers.

Allele = an alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome.

(http://biology.about.com) �

52

High Cholesterol

• High cholesterol, or hypercholesterolemia, is the result of a recessive allele (we will call it “h”).

• Homozygous dominant individuals (HH) do not have the disorder.• Heterozygous individuals (Hh)—about one in 500 people—have blood

cholesterol levels (LDL) about twice normal.

53

High Cholesterol (continued)

• Homozygous recessive individuals (hh)—about one in a million people— have very high elevated LDL cholesterol levels (about five times normal).

• LDL cholesterol can build-up in the arteries and lead to blockages, a con-dition known as atherosclerosis.

http

s://m

iddl

epat

h.co

m.a

u

54

Low-Density Lipoproteins

• Cholesterol is a lipid molecule and therefore it is not water-soluble.• Low-density lipoproteins (LDL) and high-density lipoproteins (HDL)

are carrier molecules for cholesterol to circulate in the blood.• The H allele is responsible for the production of LDL receptors in cell

plasma membranes that enable cells to uptake and breakdown cho-lesterol.

False color electron micrographwww.scienceclarified.com

55

Genetic Basis

• The HH genotype assures a full complement of LDL receptors—LDL levels in blood circulation are typically within normal limits.

• The Hh genotype has about one-half the number of LDL receptors on cells, and LDL levels are twice as high as for the HH genotype.

• The hh genotype lacks LDL receptors, allowing LDL to accumulate at very high and dangerous levels in blood circulation.

• Cholesterol-lowering drugs, such as statins, can be effective in treat-ing high LDL cholesterol.

56

Punnett Squares—Cholesterol Levels

HH

Hh Hh

hh

H H

hhParent 1 Parent 2

HH

HH HH

HH

H H

HH hh

hh hh

hh

h h

hh Hh

Hh Hh

Hh

H h

hH

Cholesterol levels:HH—low

Hh—moderately highhh—very high

Diet and exercise can also affect cholesterol

levels

57

Have you had your cholesterol (LDL and HDL) levels checked?

58

Co-Dominance

• In co-dominance, both alleles are expressed, such as in the AB blood type.

• Co-dominance is different from incomplete dominance, the expression of an intermediate trait.

59

Human Blood

• We have discussed inheritance patterns that involve two alleles— one on each chromosome of a homologous pair.

• Multiple alleles also exist for certain phenotypes, such as the ABO blood group in humans.

http

://w

ww

.cle

ocon

fere

nce.

org

60

Blood Types

• In the ABO blood group, the human blood phenotypes are A, B, AB, and O.

• A and B refer to two carbohydrates (antigens) on the surface of red blood cells (RBCs).

• RBCs may contain one carbohydrate (A or B), both carbohydrates (A and B), or neither (O).

• The presence or absence of the rhesus factor (Rh) must also be con-sidered in matching blood types—more about this later in the semes-ter.

61

Blood Type Compatibility

• Compatible blood types are critical for the transfusion of blood from donor to recipient.

• If a recipient receives a foreign blood type (A or B), antibodies in the recipient’s blood bind to the foreign carbohydrate, causing the RBCs to clump together.

• Clumping and release of hemoglobin from RBCs damage nephrons, the filtration mechanism in the kidneys.

62ht

tp://

cach

e.eb

.com

RBC Clumping

63

Three Alleles

• The four ABO blood types result from combinations of three alleles, IA, IB, and i.

• IA produces carbohydrate A, IB produces carbohydrate B, and i pro-duces neither carbohydrate.

• One of each of these three alleles is inherited from the mother and the father.

64

Combinations of Alleles

• IA and IB alleles are dominant to the i allele, but co-dominant to each other.

• The six combinations are:– IA * IA and IA * i result in type A blood. – IB * IB and IB * i result in type B blood. – IA * IB results in type AB blood where both alleles are expressed.– i * i results in type O blood—neither the A nor the B carbohydrate

is present.

65

Blood Type Predictor

http://www.testsymptomsathome.com

Try calculating these combinations using your knowledge of Mendel’s principles, co-dominance, and the alleles, IA, IB, and i.

66

http

://w

ww

.hhs

.gov

• Whole blood• Platelets• National Marrow Donor Program (http://www.marrow.org)

Blood Donor Programs

67

Do you know your blood type?

68

Pleiotropy

• So far, the examples have involved one or more genes that deter-mine one hereditary characteristic.

• In other instances, a gene can specify a number of characteristics, which is known as pleiotropy.

• A well-known instance of pleiotropy is the genetic disorder, sickle-cell disease.

69

Sickle-Cell Disease

• The hemoglobin molecules in red blood cells (RBCs) transport oxy-gen to the body’s tissues.

• In sickle-cell disease, abnormally-shaped hemoglobin molecules are produced in the bone marrow.

• The disease is due to a single amino acid mutation (valine substitutes for glutamic acid).

70

Sickle-Cell Disease (continued)

• The sickle-shaped RBCs have a greatly reduced oxygen-carrying capacity.

• It is a homozygous recessive disorder—the alleles (ss) re present on the homologous chromosomes.

71

Physical Effects

• The abnormally-linked hemoglobin molecules tend to link together and crystallize.

• When hemoglobin crystallizes, RBCs deform to a sickle shape, leading to a number of cascading symptoms.

• Crystallization is more likely to happen when blood oxygen content is low due to high altitude, physical overexertion, or respiratory ailments.

http

://trc

.ucd

avis

.edu

72

http

://w

ww

.nhl

bi.n

ih.g

ov

Sickle-Shaped RBCs

73

Breakdown of red blood cells (RBCs)

Clumping of sickled RBCs and clogging

of small blood vessels

Accumulation of sickled RBCs in the

spleen

Physical weakness Heart failure Spleen damage

Heart failure Pain and fever

Anemia Brain damage

Other organ damage

Secondary Effects

Anemia Brain damage Other organ damage

Impaired mental function

Impaired mental function

Pneumonia and other infections

Paralysis Rheumatism

Kidney failure

Cascading Symptoms

74

• Sickle-cell disease results in the premature deaths of about 100,000 people world-wide each year.

• About one in ten African Americans is heterozygous (Ss) for the gene. • It is the most common inherited disorder among African Americans,

affecting about one in 500 newborn.• The disease is rare in other ancestries.

Incidence

75

• Blood transfusions and certain drugs may relieve some of the symp-toms.

• Bone marrow transplants hold promise, and can help a person lead a productive, normal life.

Treatment

76

Can you think of other examples of pleiotropy?

77

• Mendel studied genetic characteristics that occur on an either-or-basis.• However, some characteristics, such as human skin color, vary along a

continuum in the general population.• Polygenic inheritance involves the additive effects of two or more genes

on a single phenotype characteristic.• This is the converse of pleiotropy, where a single gene can affect several

phenotype characteristics.

Polygenic Inheritance

78

http

:/cac

he.e

b.co

m

http://anthro.palomar.edu

Skin Color

79

Genetic Basis

• Let’s say, hypothetically, that skin color is completely determined by only three genes, each inherited separately.

• Dark-skin alleles (A, B, and C) each contributes one unit of darkness.• Light-skin alleles (a, b, and c) each contributes one unit of lightness.• Each dark-skin allele is incompletely dominant to the light-skin alleles.

Units of skin darkness:A = B = C

Units of skin lightness:a = b = c

80

Combinations of Alleles

• A person who has AABBCC would have very dark skin, while a person who has aabbcc would have very light skin.

• A person who has AaBbCc would have skin of an intermediate shade.• Because the six alleles have a simple additive effect, AaBbCc would

produce the same skin color as AABbcc.• Sixty-four genotype combinations are possible in this simplified model,

resulting in seven shades of skin color.

81

A Simplified Inheritance Model

F1 generation

F2 generation

P generation AABBCC x aabbcc

Histogram and bell-shaped distribution of

skin shades

http://fig.cox.miami.edu

F1 outcomes: 1 intermediate skin shade

F2 outcomes:

1/64 (very light skin)6/6415/6420/64 (intermediate skin shade)15/646/641/64 (very dark skin)

Total = 64/64

82

• Many more shades of skin color are possible than the seven depicted in the model.

• Intermediate shades of skin color are also determined by environmental factors such as sunlight exposure.

• Thus, the genetic basis of skin color is not the entire story no matter how well the genes are described.

Environmental Factors

83

• Some human phenotypes result from the interaction of genetics and environment.

• Some phenotypes, such as eye color, are fully genetically-determined.• Other phenotypes, such as height, have an environmental component

(for example, diet during childhood).• Human gender identity and sexual orientation are part of the ongoing

debate about the role of genetics versus environment, or “nature ver-sus nurture.”

Genetics and the Environment

84

Penetrance

• Some dominant alleles are not always consistently expressed in the phenotype.

• The probability that a person having a dominant allele will display the associated phenotype is known as its penetrance.

• In complete penetrance, the associated phenotype is always displayed (p = 1.00).

• In incomplete penetrance, the phenotype may or may not be shown (p < 1.00).

p = probability, which ranges between 0.00 and 1.00.

85

• The BRCA1 gene associated with a rare form of breast cancer is in-completely penetrant.

• About 70 percent of women with the gene will develop breast cancer by age 70.

• Thus, BRCA1 is said to be 70 percent penetrant.• Women with the gene should be screened regularly for early detection

of the disease.

BRCA1 Gene

86

Expressivity

• The degree to which an allele expresses a phenotype can vary from person-to-person.

• Polydactyly is a genetic condition where an individual can have more than ten fingers or toes.

• This condition shows variable expressivity—some persons with the allele have additional fully functional fingers or toes while others have skin tags.

http

://up

load

.wik

imed

ia.o

rg

87

Can you describe the differences between penetrance and expressivity?

88

Chromosomal Basis of Inheritance

• Mendel published his research in 1866; researchers, were only able to establish the genetic processes a few decades later.

• They noticed parallels between chromosomes and Mendel’s inheritance factors at the beginning of the 20th century.

• The chromosomal basis of inheritance, a major axiom in biology, began to emerge.

The axiom states:

1. All genes are located on the chromosomes.2. The behavior of homologous chromosomes during meiosis

and fertilization accounts for the inheritance patterns from parents to their offspring.

Axiom = an established rule, principle, or law.

89

Electron micrograph (false color image)http://www.amnh.org

Homologous Chromosomes

90

• Two or more genes located near each other on a chromosome tend to be inherited together.

• One instance in Mendel’s work involved flower color and pollen shape in pea plants.

• The F2 plants did not show the expected ratio predicted for a dihybrid cross.

Linked Genes

91

• The ratio that was observed is the result of crossing-over patterns of the chromatids during meiosis I.

• Linked genes that cross-over together produce phenotypes that cannot be predicted by the principles of segregation and independent assortment.

Linked Genes (continued)

92

Fruit Flies

http

://fly

base

.net

Drosophila melanogaster

93

• The fruit fly, Drosophila melanogaster, can be inexpensively raised, and can produce several generations within a few months.

• Among other research uses, the fruit fly is used in genetics to map genes on chromosomes.

Research Uses

94

• The farther apart two genes are on homologous chromosomes, the more likely they will display genetic recombination since there are more points where crossing-over can occur.

• The crossing-over patterns can be used to determine the relative location of genes on chromosomes to develop linkage maps.

• Prior to genome mapping, observation of crossing-over patterns was the primary method for developing maps of genes residing on chromosomes.

Genetic Recombination

95

Sex-Linked Genes

• We briefly discussed the role of the X and Y chromosomes in sexual differentiation as female or male—more on this later in the semester.

• The X chromosome also carries genes for characteristics unrelated to genetic sex.

• A gene located on the X chromosome is known as a sex-linked gene.

http

://w

ww

.san

ger.a

c.uk

96

• The X chromosome, due its much larger size, carries many more genes than the Y chromosome.

• The X chromosome has what are known as sex-linked genes unrelated to sexual differentiation.

• The Y chromosome carries few genes, in large part because it is so small.

• Experiments have been conducted with fruit flies to determine how sex-linked genes determine the genotypes and phenotypes of their offspring.

Role of the X Chromosome

97

• The X chromosome has somewhere between 900 and 1,200 genes— many of the genes are involved in human development in both sexes.

• Only one of the genes (DAX1) is involved in female sexual differentia-tion.

• Other genes involved in determining the female phenotype are on the autosomal chromosomes (the other 22 pairs).

Genes on the X Chromosome

98

• The SRY gene on the Y chromosome is involved in male sexual differ-entiation.

• Other genes on the Y chromosome are involved in male sexual function and fertility.

• A Y-linked trait will be expressed if the Y chromosome is present since the Y chromosome is hemizygous.

• That is, one copy of the allele is present and passed from the father.

Genes on the Y Chromosome

99

• Hairy ears is one of a small number of Y-linked traits that is not related to sexual function.

• This allele is said to be incompletely penetrant since not all hairy-eared men have sons with hairy ears although the allele is passed with the Y chromosome.

• The amount of ear hair can vary from slight- to very-hairy due to variable expressivity.

Genes on the Y Chromosome (continued)

100

Sex-Linked Disorders

• Some human genetic disorders are the result of recessive alleles on the X chromosome.

• A male needs to inherit one of these sex-linked alleles from his mother, while a female would need one from each parent, a much rarer situation.

• Thus, males are far more often afflicted by sex-linked disorders, including red-green color blindness, hemophilia, and Duchenne muscular dystro-phy.

101

http://www.medgadget.com

Cross-section through the retina of the human

eye

Electron micrograph of a small group of rods and

cones.

ww

w.e

yede

sign

book

.com

Rods and Cones

102

• Red-green color blindness is a fairly common sex-linked disorder in males, although its severity can vary (due to variable expressivity).

• In some affected people, red or green hues may appear to be gray, while in others, confusion may exist over different shades of these colors.

• Red-green color blindness results from the malfunctioning of the red and green in the retina of the eye.

• Although males are usually affected, a small number of females may have the problem if they have the recessive gene on both X chromo-somes, which is a rare event.

Red-Green Color Blindness

103ht

tp://

ww

w.m

edia

colle

ge.c

om

What embedded figure do you see?

Ishihara Color Plate

104

• Hemophilia is another sex-linked recessive disorder—it effects are almost always limited to males since only one copy of the allele is needed.

• Persons afflicted with this disorder bleed excessively when bruised or otherwise injured.

• Excessive bleeding is due to an abnormal allele on the X chromosome for producing factors VII and IX that enable blood to clot.

Hemophilia

105

Victoria, Queen of England

http

://w

ww

.btin

tern

et.c

om

1819-1901

106

• In the 18th century, hemophilia plagued the royal families of Europe, who were often closely related through intermarriage.

• The first royal family member who was known to have hemophilia was the son of Queen Victoria of England.

• The allele may have occurred as a spontaneous mutation in one of the gametes (egg or sperm) of Victoria’s mother or father that was passed by Victoria to her children.

A Famous Case Study

107

• Hemophilia was introduced into the royal families of Prussia, Russia, and Spain through the marriage of Victoria’s daughters, who carried the recessive gene.

• Queen Victoria’s granddaughter, Alexandra, was married to the last Czar of Russia, Nicholas.

• Through an analysis of family pedigree, it was later demonstrated that Alexandra was a carrier of the recessive gene, as were her mother and grandmother (Queen Victoria).

Nicholas and Alexandra

108

• Alexandra and Nicholas’s son, Alexis, was known to have had hemo-philia.

• The family met a tragic end in the overthrow of the Russian Czar in the early 20th century.

Nicholas and Alexandra (continued)

109

Family Pedigree

Solid-circle-within-a-circle—carrier of X-linked recessive gene.Blue square—afflicted with hemophilia.

http

://bi

o340

0.ni

cerw

eb.c

om

110

• Duchenne muscular dystrophy is characterized by a progressive weak-ening and loss of skeletal muscle.

• Almost all cases of this sex-linked genetic disorder involve males for the same reasons we discussed.

• The initial symptoms, including difficulty in standing-up, appear in early childhood.

• The child may require a wheelchair by age 12 due to a continued weak-ening of skeletal muscles and difficulty in breathing, which is controlled by skeletal muscles.

Duchenne Muscular Dystrophy

111

• In the United States, one in 3,500 male newborn is affected by muscu-lar dystrophy.

• The rate is much higher in some closed populations such as the Amish.• In one Amish community in Indiana, one out of 100 newborn males has

the disorder.• DNA technology was used to map the gene to the X chromosome.

Incidence

112

http

://w

ww

.val

po.e

du

http://riversaredamp.files.wordpress.com

Road sign,southeasternPennsylvania

Amish Communities in the United States

113

Pennsylvania Amish Country

http://www.baltimoresun.com

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.

http://1001arabian.netQuickTime™ and a

TIFF (Uncompressed) decompressorare needed to see this picture.

http://www.lindamyers.com

114

Have you met anyone who has one of these sex-linked disorders?