Mendelian Inheritance & Beyond

CHAPTER 4 & 5

INHERITANCE• We marvel at physical

resemblances, as well as at talents, interests, and quirks that seem to run in families.

• Parents and offspring often share observable traits.

• Grandparents and grandchildren may share traits not seen in parents.

• Why do traits disappear in one generation and reappear in another?

• Genetics the science of heredity.

• Heredity : The passing on of traits (CHARACTERISTICS) from PARENTS to OFFSPRING.

TRAIT• Any CHARACTERISTIC of an organism.

• EX: hair color, eye color, spots on a cheetah, skin color, freckles, dimpled chin, *breast cancer susceptibility, *alcoholism susceptibility

• All traits are located on chromosomes, IN PAIRS each trait has a certain segment of DNA: This segment is a GENE.

• People have always wondered at their similarities –and fought over their differences.

• 7000 years ago early humans began the practice of SELECTIVE BREEDING in both plants and animals.

• FARMERS in Mexico used genetic knowledge 6,000 years ago when they set aside seed from the hardiest plants of wild grass and used it to plant the next years crop. Eventually, they breed domestic CORN.

GREGOR MENDEL1822-1884 : Augustinian monk & teacher, Gregor

Mendel experimented with pea plants in the monastery gardens

• The father of modern genetics

• Combined

• Plant Breeding

• Statistics

• Careful recordkeeping

• Described hypothesis of transmission of traits now considered laws of inheritance

• Mendel’s principles if inheritance formed the FOUNDATION for the development of genetics and much of modern biology.

GREGOR MENDEL• It took him 2 years to select the pea plant as

his subject.

• He collected data for 8 years.

• His sample sizes were large; he tabulated results from 28,000 pea plants.

• He repeated his experiments.

• He analyzed his data with statistics (probability theory).

• In 1865 he made his work public about heredity.

• His work was not well known until early 1900s—34+ years later!

WHY PEAS?

• Mendel selected peas because:

• He had ACCESS to varieties that differed in OBSERVABLE alternative characteristics.

• His earlier studies of flower structure indicated that peas usually reproduce by SELF-POLLINATION, so he could easily CONTROL their pollination.

MENDEL STUDIED PEA TRAITS WITH TWO DISTINCT FORMS

TRUE BREEDING PLANTS

Plants which

consistently have

offspring with same

trait as parent are true

breeding plants.

• Parents Generation - P

• Second Generation – F1

• Third Generation – F2

• Mendel first performed MONOHYBRID CROSSes of pea plants that were PURE for a single trait, like height.

• Crossing PURE TALL pea plants with PURE SHORT pea plants resulted in all of the next generation (F1) being TALL.

Progeny show only one form of the trait.

The observed trait is called dominant.The masked trait is called recessive.

• When Mendel let the “kids”(F1) Self-Pollinate, the short trait REAPPEARED in the “grandkids”.

• The “short” TRAIT had skipped a generation because it was hidden by the “Tall” TRAIT

MENDEL’S PRINCIPLES BECAME THE LAWS OF INHERITANCE

• Inheritance involves the passing of discrete units of inheritance, or genes, from parents to offspring.

• Dominant alleles mask recessive alleles.

1. The Law of Segregation

• During reproduction, the inherited factors (now called alleles) that determine traits are separated into reproductive cells by a process called meiosis and randomly reunite during fertilization.

2. The Law of Independent Assortment

• Genes located on different chromosomes will be inherited independently of each other.

LAW OF SEGREGATION

• Why do traits “disappear” in one generation only

to reappear in a subsequent generation?

• Each plant possesses two distinct separable units (alleles) for each trait inherited from each parent.

• Gametes contain ONE allele for each trait.

• Only one version is observed in an individual.

• The unit (allele) does not disappear.

• It may be present but hidden.

LAW OF SEGREGATION

LAW OF SEGREGATION

In sperm and egg, only one allele for a trait is passed on

Gg

G g G g

Gg

LAW OF SEGREGATION: THE MONOHYBRID CROSS

Two heterozygous parents produce gametes

with T or t allele equally frequently.

Offspring genotypes 1/4 TT : 1/2 Tt : 1/4 tt

Offspring phenotypes 3/4 tall : 1/4 short

DOMINANT AND RECESSIVE ALLELESa. An ALLELE is a particular version of a gene.

Alleles arise due to mutations in DNA. Mendel’s “elementen”

b. Alleles arise due to mutations.

c. Differ in sequence at one or more sites.

d. Capital letters are dominant alleles, and always show through

e. Lower case letters are recessive alleles, and are masked by the dominant allele

GENOTYPE VS PHENOTYPE

Genotype , 2 alleles make up one genotype

• the genotype is the allele sequence for the trait

• Homozygous Dominant — two dominant alleles = BB

• Heterozygous — one dominant and one recessive allele = “hybrid” = Bb

• Homozygous Recessive — two recessive alleles = bb

* homozygous = “true-breeding”

GENOTYPE VS PHENOTYPE

• Phenotype, what the genotype says. What is expressed or seen.

• Putting the genotype into words

• EX:

• BB = Brown eyes

• Bb = Brown eyes

• bb = Blue eyes

• Wildtype phenotype = Most common phenotype

• Mutant phenotype = Phenotype different from the wildtype

• Wildtype allele = Most frequent allele associated with the common phenotype

• Mutant allele = Allele associated with the mutant phenotype

WILDTYPE= most common version in the general population

PROBABILITY & PUNNETT SQUARES

PROBABILITYThe likelihood that an event will occur.

# on die probability

1 1/6

2 1/6

3 1/6

4 1/6

5 1/6

6 1/6

The probability of an event

= # of chance of event total possible events

The probabilities of all the possible events add up to 1.

•No chance of event probability = 0(e.g. chance of rolling 8 on a six-sided die)

•Event always occurs probability = 1 (chance of rolling 1,2,3,4,5,or 6 on a six-sided die)

PROBABILITY

• Parents Generation - P

• Second Generation – F1

• Third Generation – F2

• Each probability is the same with EACH pregnancy!• Every time a women and man get pregnant, they have the same

probability!

PROBABILITY EXAMPLES• Parent Generation:

• Heterozygote

• Homozygous Dominant

• What are the possible F1 results?

• What are the genotype probability?

• BB – 50%

• Bb – 50%

• bb - 0%

• Dominant Offspring – 100%

• Recessive Offspring – 0%

• GENOTYPIC RATIO: 1:1

• PHENOTYPIC RATIO: 4:0

B B

B BB BB

b Bb Bb

EXAMPLE – F1 GENERATION• A man with a widow's peak (WW)

marries a woman with a continuous hairline (ww). A widow's peak is dominant over a continuous hairline. What kind of hairline will their children have?

• P1 Alleles?• WW & ww

• F1 Generation?

• Genotype: Phenotype:• WW – _______ _____________

• Ww – _______ ______________

• ww – _______

W W

w Ww Ww

w Ww Ww

CONTINUE EXAMPLE – F2 GENERATION

W w

W WW Ww

w Ww ww

• Suppose one of their children (Ww) marries someone who is also heterozygous (Ww). What type of hairline will their children have?

• F2 Generation Genotype:• WW – 25%

• Ww – 50%

• ww – 25%

• RATIO – 1:2:1

• F2 Generation Phenotype:• Widows Peak – 75%

• Continuous Hairline – 25%

• RATIO – 3:1

• This is ONLY true IF both parents were Heterozygous!

EXAMPLE 2 – REAL WORLD DISEASE

• Jane and John are expecting a baby and know that they are both carriers (ie heterozygous) of cystic fibrosis (Cc). What is the probability that their child will have cystic fibrosis (cc)? What is the probability that their child will be a carrier of cystic fibrosis?

• Chance of child being:

• ________% Disease free Genotype:

• ________% Cystic fibrosis carrier Genotype:

• ________% Cystic fibrosis Genotype:

MODE OF INHERITANCE

indicates the patterns with which the mutant

phenotype is associated.

Most common Autosomal recessive Autosomal dominantX-linked recessiveX-linked dominantY-linkedmitochondrial

AUTOSOMAL DOMINANT INHERITANCE

• Heterozygotes exhibit the affected phenotype.

• Males and females are equally affected and may transmit the trait.

• Affected phenotype does not skip generation.

AUTOSOMAL RECESSIVE INHERITANCE• Heterozygotes carry the

recessive allele but exhibit the wildtype phenotype.

• Males and females are equally affected and may transmit the trait.

• May skip generations.

COMPARISON OF AUTOSOMAL DOMINANT AND AUTOSOMAL RECESSIVE INHERITANCE

NoYesAt least one parent of affected child must be affected?

YesNoTrait skips generations?

YesYesMales and females transmit the trait?

YesYesMales and females affected?

Autosomal recessive

Autosomal dominant

LAW OF INDEPENDENT ASSORTMENT

• Two genes on different chromosomes segregate their alleles independently.

• The inheritance of an allele of one gene does not influence which allele is inherited at a second gene.

• Another way to look at this is, whether a flower is purple has nothing to do with the length of the plants stems – each trait is independently inherited.

• We now know that this segregation of alleles occurs during the meiosis.

LAW OF INDEPENDENT ASSORTMENT

INDEPENDENT ASSORTMENT OF TWO TRAITS• In a dihybrid cross, parents with two differing

traits are crossed.

• Which allele is dominant?

Heterozygous peas are round and yellow.

Therefore round is dominant to wrinkled yellow is dominant to green

TWO TRAITS SEGREGATING INDEPENDENTLY

TWO TRAITS SEGREGATING INDEPENDENTLY

315 round yellow peas

108 round green peas

101 wrinkled yellow peas

32 wrinkled green peas

416

140

2.97 :1

423

133

3.18 : 1

DIHYBRID CROSSES

**Crossing 2 different traits at the same time

PROBABILITY OF INDEPENDENT EVENTSThe probability of independent events is calculated

by multiplying the probability of each event.

In two rolls of a die, the chance of rolling the number 3 twice:

Probability of rolling 3 with the first die = 1/6

Probability of rolling 3 with the second die = 1/6

Probability of rolling 3 twice = 1/6 x 1/6 or 1/36

PROBABILITY OF INDEPENDENT EVENTS• What is the chance of an

offspring having the

homozygous recessive

genotype when both parents

are doubly heterozygous?

PROBABILITY OF DEPENDENT EVENTSThe probability of dependent events is calculated

by adding the probability of each event.

In one roll of a die, what is the probability of rolling either the number 5 or an even number?

Probability of rolling 5 or an even number = 1/6 + 3/6 or 4/6

Probability of rolling the number 5 = 1/6

Probability of rolling an even number = 3/6

PROBABILITY OF DEPENDENT EVENTS

Parents are heterozygous for a trait, R.

What is the chance that their child carries

at least one dominant R allele?

Probability of child carrying RR = 1/4Probability of child carrying Rr = 1/2

Probability of child carrying R_ = 1/4 + 1/2 = 3/4

B = black

b = white

H = Hairy

h = no hair

* Determine genotype for parentsParents must have 4 alleles (aka 4 letters)

Heterozygous black, hairless male = _______

White heterozygous hairy female = ________

HOW TO DETERMINE THE PROBABILITY FOR MORE THAN ONE TRAIT

• Draw the punnett square with 16 boxes.

• Separate the parental alleles into 2 groups & Foil so that all possible ALL combinations are represented

Bbhh =

bbHh =

Put parent gamete combinations on box

Bbhh gametes:

Bh, Bh, bh, bh

bbHh gametes:

bH, bh, bH, bh

Bh Bh bh bh

bH

bh

bH

bh

BbHh BbHh bbHh bbHh

Bbhh Bbhh bbhh bbhh

BbHh BbHh bbHh bbHh

Bbhh Bbhh bbhh bbhh

Determine the Genotype and Phenotype Ratio

Genotype:

4 BbHh : 4 bbHh : 4 Bbhh : 4 bbhh

Phenotype:

4 Black and Hair :

4 White and Hair :

4 Black and Hairless :

4 White and Hairless

SAMPLE PROBLEM

Genotype Ratio: ___ RRYY : ___ RRYy : ___ RrYY : ___ RRyy : ___ RrYy : ___ rrYY : ___ Rryy : ___ rrYy : ___ rryy

Phenotype Ratio : ___ Round and Yellow : ___ Round and Green :

___ Wrinkled and Yellow : ___ Wrinkled and Green

SAMPLE PROBLEM

Genotype Ratio: 1 RRYY : 2 RRYy : 2 RrYY : 1 RRyy : 4 RrYy : 1 rrYY : 2 Rryy : 2 rrYy : 1 rryy

Phenotype Ratio : 9 Round and Yellow : 3 Round and Green : 3 Wrinkled and Yellow : 1 Wrinkled and Green

PRACTICE PROBLEM

Determine the genotype of the following bunnies:

Heterozygous Black-Hairy:_________

White hairless: ____________

PRACTICE PROBLEM

Determine the gamete combinations

BbHh: _______________________________

bbhh: _______________________________

PRACTICE PROBLEMComplete the punnett square:

PRACTICE PROBLEMComplete the punnett square:

BH Bh bH bh

bh

bh

bh

bh

PRACTICE PROBLEMComplete the punnett square:

BbHh Bbhh bbHh bbhh

BbHh Bbhh bbHh bbhh

BbHh Bbhh bbHh bbhh

BbHh Bbhh bbHh bbhh

BH Bh bH bh

bh

bh

bh

bh

PRACTICE PROBLEM

Give the genotype ratio:

Give the phenotype ratio:

4 BbHh : 4 Bbhh : 4 bbHh : 4 bbhh

4 Black and Hair : 4 Black and Hairless :

4 White and Hair: 4 White and Hairless

CROSS MULTIPLYING METHOD• A Shorter way

• Mendelian genetics reflect the laws of probability

• Mendel's laws are basically real-life applications of the rules of probability that apply to a coin toss, rolling a dice, or drawing from a deck of cards

• Make monohybrid cross punnett squares for each trait and multiply the fractions for each result (independently sort).

• Make monohybrid cross punnett squares for each trait and multiply the fractions for each result.

• Phenotypes = Add up all the genotypes that code for the same phenotype.

CROSS MULTIPLYING METHOD (SHORT)

EXAMPLE #2

• In this example Brown eyes (B) are dominant to blue eyes(b) and Almond shaped eyes (A) are dominant to round eyes (a).

• Homozygous dominant brown eyes with heterozygous almond shape mates with Heterozygous brown eyes with round shape.

• List the genotypic and phenotypic ratios for the offspring.

Ex:B= Brown eyesb = blue eyesA= Almond shapea = round shape

PEDIGREES

PEDIGREESSYMBOLIC REPRESENTATIONS OF FAMILY RELATIONSHIPS AND INHERITANCE OF A TRAIT

AUTOSOMAL DOMINANT INHERITANCE OF BRACHYDACTYLY

HETEROZYGOTES EXHIBIT THE PHENOTYPE.

AUTOSOMAL RECESSIVE INHERITANCE OF ALBINISM

HETEROZYGOTES CARRY THE RECESSIVE ALLELE BUT EXHIBIT THE WILDTYPE PHENOTYPE

GENETIC PREDICTIONS

What is the chance that Ellen’s child has a sickle cell anemia allele (a)?

Ellen Michael

?

Ellen and Michael’s parents must be carriers.

A a

A

a

AA Aa

Aa aa

Ellen is not affected andcannot carry aa genotype

chance child inherits Cystic fibrosis = 1/2

Overall chance child carries Cystic fibrosis allele from Ellen = 2/3 x 1/2 = 1/3

chance Ellen is a carrier = 2/3

Ellen’s brother Michael hasCystic fibrosis, an autosomal recessive disease.

EXCEPTIONS TO MENDEL’S LAW

EXCEPTIONS TO MENDEL’S LAW• There are some exceptions to Mendel’s principles, which have been

discovered as our knowledge of genes and inheritance has increased. The principle of independent assortment doesn’t apply if the genes are close together (or linked) on a chromosome. Also, alleles do not always interact in a standard dominant/recessive way, particularly if they are codominant or have differences in expressivity or penetrance.

• Mendel’s traits showed two distinct forms

• Most genes do not exhibit simple inheritance

• Genotypic ratios persist but phenotypic ratios may vary due to “outside-the-gene” influences including - Multiple alleles

- Other nuclear genes

- Non-nuclear genes (next unit)

- Gene linkage (next unit)

- Environment (next unit)

LETHAL ALLELESA lethal genotype causes death before the individual can reproduce

- This removes an expected progeny class following a specific cross

A double dose of a dominant allele may be lethalExamples:

- Achondroplastic dwarfism

- Mexican hairless dogs• Homozygous Dominant = dies

• Heterozygous = little person

• Homozygous recessive = normal

-

Figure 5.1b

Figure 5.1

Lethal Alleles

MULTIPLE ALLELES• An individual carries two alleles for each autosomal

gene

• However, a gene can have multiple alleles because its sequence can deviate in many ways

• Different allele combinations can produce variations in the phenotype

- PKU gene has hundreds of alleles resulting in four basic phenotypes

- CF gene has over 1500 alleles

INCOMPLETE DOMINANCE

• Incomplete Dominance: is a condition in which the dominant allele cannot completely mask the expression of another allele.

• The heterozygote phenotype is somewhere between that of two homozygotes.

• For example, red-flowered snapdragons crossed with white ones yield pink in the first generation.

Example: Familial hypercholesterolemia (FH)

- A heterozygote has approximately half the normal number of receptors in the liver for LDL cholesterol

- A homozygous for the mutant allele totally lacks the receptor, and so their serum cholesterol level is very high

IncompleteDominance

PinkA blend of dominant and recessive traits

INCOMPLETE DOMINANCE

Figure 5.2

Genetics

BLOOD

• What kind of blood type do you have?

• How do you know this information!

• What is in blood?

• Why is it important?

• What is its function?

BLOOD TYPING IS DETERMINED BY THE RED BLOOD CELLS!

What is the function of red blood cells?

Transport Oxygen & Carbon Dioxide Gases!!

WHAT MAKES UP OUR BLOOD?• RED BLOOD CELLS (Erythrocytes) – The most abundant

cells in our blood; they are produced in the bone marrow and contain a protein called hemoglobin that carries oxygen to our cells.

• WHITE BLOOD CELLS (Leukocytes) – They are part of the immune system and destroy infectious agents called pathogens. Produce antibodies

• PLASMA – This is the yellowish liquid portion of blood that contains electrolytes, nutrients and vitamins, hormones, clotting factors, and proteins such as antibodies to fight infection. More than 92% of plasma is water.

• PLATELETS (Thrombocytes) – The clotting factors that are carried in the plasma; they clot together in a process called coagulation to seal a wound and prevent a loss of blood.

BLOOD FACTS

The average adult has about FIVE liters of blood inside of their body, which makes up 7-8% of their body weight.

Blood is living tissue that carries oxygen and nutrients to all parts of the body, and carries carbon dioxide and other waste products back to the lungs, kidneys and liver for disposal. It also fights against infection and helps heal wounds, so we can stay healthy.

There are about one billion red blood cells in two to three drops of blood. For every 600 red blood cells, there are about 40 platelets and one white cell.

GENETICS OF BLOOD TYPES

• Your blood type is established before you are BORN, by specific GENES inherited from your parents.

• These two genes - one gene from your MOTHER and one from your FATHER -determine your blood type by causing proteins called AGGLUTINOGENS to exist on the surface of all of your red blood cells.

CODOMINANCE• Codominance: is a condition in which both alleles are

expressed in heterozygotes.

• It is NOT a middle combination of two alleles like the red and white snapdragons make pink.

• Instead it is where both alleles and their traits are both equally expressed. Best example is blood type.

• The ABO gene encodes a cell surface protein

- IA allele produces A antigen

- IB allele produces B antigen

- i (IO) allele does not produce antigens

• Alleles IA and IB are codominant, and both are completely dominant to i (type O). Therefore, some persons can express both genes and have AB blood.

WHAT ARE BLOOD TYPES?There are 3 alleles or genes for blood type: A, B, & O. Since we have 2 genes, there are 6 possible combinations.

Blood Types

IAIA or IAi = Type AIAIA or IAi = Type B

ii= Type OIAIB = Type AB

Figure 5.3

Figure 5.4

Offspring from Parents with Blood Type A and Blood Type B

Figure 5.4

BLOOD TYPE TESTING!

How common is your blood type?

OUT OF 100 DONORS . . . . .• 84 donors are RH+

• 16 donors are RH-

• 38 are O+

• 7 are O-

• 34 are A+

• 6 are A-

• 9 are B+

• 2 are B-

• 3 are AB+

• 1 is AB-

There is always a need for Type O donors because their blood may be transfused to a person of any blood type in an emergency.

About half of all blood ordered by hospitals is Type O blood.

You can start donating blood at age 18.If you have a planned surgery-you can bank your own blood ahead of time.

RH FACTORS

• Scientists sometimes study Rhesus monkeys to learn more about the human anatomy because there are certain similarities between the two species. While studying Rhesus monkeys, a certain blood protein was discovered. This protein is also present in the blood of some people. Other people, however, do not have the protein.

• The presence of the protein, or lack of it, is referred to as the Rh (for Rhesus) factor.

• If your blood does contain the protein, your blood is said to be Rh positive (Rh+). If your blood does not contain the protein, your blood is said to be Rh negative (Rh-).

A+ A-B+ B-

AB+ AB-O+ O-

What type of blood does this person have?

If your blood type is . . .

Type You Can Give Blood To

You Can Receive Blood From

A+ A+  AB+ A+  A-  O+  O-

O+ O+  A+  B+  AB+ O+  O-

B+ B+  AB+ B+  B-  O+  O-

AB+ AB+ Everyone

A- A+  A-  AB+  AB- A-  O-

O- Everyone O-

B- B+  B-  AB+  AB- B-  O-

AB- AB+  AB- AB-  A-  B-  O-

HAEMOLYSIS – USED TO BE A MAJOR CAUSE OF STILLBIRTH• The newborn baby becomes jaundiced during the first 24 hours of life

(due to excess bilirubin in the blood) and slightly anaemic. In more severe cases, the level of bilirubin in the blood may increase to a dangerous level, causing a risk of brain damage. The most severely affected babies have marked anaemia while still in the uterus, become very swollen, and are often stillborn. Treatment = early delivery of baby or possibly fetal transfusions.

• Mother who is Rh- has a baby who is Rh+. During the 1st babies birth, some of the babies blood gets into the mother blood stream. Mother develops an immune response to Rh + blood.

• Since the 1970s, Rh - mothers are given the Anti D injection following a babies birth. This will seek out the babies blood cells so that the mother does not have a chance to develop an immune response.

•

EXAMPLE: TWO PARENTS ARE AB AND O BLOOD TYPE, WHAT ARE THE GENOTYPES AND PHENOTYPES OF THEIR CHILDREN?

Blood TransfusionsA blood transfusion is a procedure in which blood is given to a patient through an intravenous (IV) line in one of the blood vessels. Blood transfusions are done to replace blood lost during surgery or a serious injury. A transfusion also may be done if a person’s body can't make blood properly because of an illness.

Who can give you blood?

People with TYPE O blood are called Universal Donors, because they can give blood to any blood type.

People with TYPE AB blood are called Universal Recipients, because they can receive any blood type.

Rh + Can receive + or - Rh - Can only receive -

Universal Donor

Universal Recipient

MICROSCOPIC VIEWS

Bird Blood

Cat Blood

Dog Blood

Fish Blood

Frog Blood

Snake BloodHuman Blood

Horse Blood

EPISTASISThe phenomenon where one gene affects the expression

of a second gene

Example: Bombay phenotype

- The H gene is epistatic to the I gene

- H protein places a molecule at the cell surface to which the A or B antigens are attached

- hh genotype = no H protein

- Without H protein the A or B antigens can not be attached to the surface of the RBC

- All hh genotypes have the phenotype of type O, although the ABO blood group can be anything (A, B, AB, or O)

PENETRANCE AND EXPRESSIVITY• Penetrance refers to the all-or-none expression of a

single gene

• Expressivity refers to the severity or extent

• A genotype is incompletely penetrant if some individuals do not express the phenotype

• A phenotype is variably expressive if symptoms vary in intensity among different people

PLEIOTROPY• The phenomenon where one gene controls several functions or

has more than one effect

Example: Porphyria variegata

- Affected several members of European Royal families, including King George III

- The varied illnesses & quirks appeared to be different unrelated disorders

Photo © North Wind Picture Archives

Figure 5.5a

Figure 5.5b

Pleiotropy

Figure 5.5

THE PORPHYRIAS• Diseases that result from deficiencies of any of

several enzymes required to make heme

• In each disease, an intermediate biochemical builds up

- It may be excreted in urine, or accumulate in tissues causing symptoms

- These symptoms, including reddish teeth and photosensitivity, may have inspired the vampire and werewolf legends

Figure 5.6

Figure 5.7

GENETIC HETEROGENEITY

• Different genes can produce identical phenotypes

- Hearing loss – 132 autosomal recessive forms

- Osteogenesis imperfecta – At least two different genes involved

- Alzheimer disease – At least four different genes involved

• Genes may encode enzymes that catalyze the same biochemical pathway, or different proteins that are part of the pathway

Figure 5.8

PHENOCOPY• A trait that appears inherited but is caused by the

environment• May have symptoms that resemble an inherited trait or

occur within familiesExamples:

- Exposure to teratogens- Thalidomide causes limb defects similar to

inherited phocomelia- Infection

- AIDS virus can be passed from mother to child, looking like it is inherited

THE HUMAN GENOME SEQUENCE ADDS PERSPECTIVE

The Human Genome Project has revealed that complications to Mendelian inheritance are more common than originally thought

Thus terms like epistasis and genetic heterogeneity are beginning to overlap and blur- Example: Marfan syndrome

Interactions between genes also underlie penetrance and expressivity- Example: Huntington disease

Table 5.1