lecture notes Nov 13

Nov 13 Chapter 9 Patterns of Inheritance (continued)

ii) genetic recombination

In reality, F2 generation always contains a small proportion of recombinant phenotypes due to crossing over.

Crossing over produces new combinations of alleles (Fig 9.19A, p175).

In the example of sweet pea plants, crossing over would produce gamete genotypes such as Pl and pL.

As a result, about 10 % of F2 generation shows recombinant phenotype (Fig 9.18, p174).

Can you identify recombinant phenotypes in the Fig 9.18?

iii) recombination frequency vs. genetic map

Recombination frequency - the percentage of recombinants in offspring.

Recombination frequency (%) =

(number of recombinant / total number of offspring) x 100

ex. Fig 9.18

number of recombinant 21 + 21= 42

total number of offspring 284+21+21+55= 381

recombination frequency 42 / 381 = 11 %

- Recombinant frequency is higher between genes located further apart in the chromosome.

- Physical distances between gene loci can be estimated via recombination frequency (Fig 9.20, p176) ® Genetic map

Example:

If recombination frequencies between three genetic loci A, B and C are

A and B 20 %

B and C 15 %

C and A 5 %

Genetic map of loci A, B and C would be:

f. sex-linked genetic disorders

i) determination of sex

- Many (but not all) animals have two separate sexes.

- Many (but not all) animals that have sexes contain sex chromosomes.

- Human sex is determined by X and Y chromosomes (the X-Y system, Fig 9.21A, p177).

XX – female

XY – male

The Y chromosome carries genes necessary for male development.

Fruit fly: XX – female XY – male

Crickets, grasshoppers: XX – female XO – male

Bird, butterflies: ZW – female ZZ – male

Bee, ants: diploid – female haploid – male

- Some animals can develop into both male and female.

- Some animals and most plants do not have separate sexes at all. Individuals produce both male and female sexual organs.

ii) sex-linked genetic disorders

- Red-green color blindness, hemophilia and Duchenne muscular dystrophy are examples of sex-linked genetic disorders.

- They are localised on the X chromosome and exhibit a unique pattern of inheritance.

- These disorders affect mostly males.

Sex-linked alleles

X^A – dominant allele

X^a – recessive allele

Example: Red-green color blindness X^cb

X^cb– color blind allele X^CB – normal vision allele

Genotype of a female carrier: X^CBX^cb

Genotype of a normal male: X^CBY

Children of a female carrier and a normal male:

Genotype

	X^CB	X^cb
X^CB	X^CBX^CB
Y

Phenotype

	X^CB	X^cb
X^CB	normal female
Y

Probability of a female child being color blind:

Probability of a male child being color blind:

5) Genetic testing

- Genetic testing is becoming more and more common.

- > 900 genetic disorders can be tested today.

- Detects presence and absence of defective alleles or genetic markers.

- The presence of a defective allele does NOT mean the person has the disease.

ex1. A person with the Huntington’s disease allele may not develop the disease

until later in life.

ex2. A person with a breast cancer gene has a higher risk of developing breast

cancer but that does not mean that she has cancer.

Different types of genetic testing

a. Diagnostic testing allows accurate diagnosis of patients showing symptoms.

b. Newborn screening is detection of genetic disorders immediately after birth. It allows affected infants to receive immediate medical attention.

ex. Phenylketonuria (PKU): Defect in metabolism of amino acid phenylalanine. Requires nutritional restrictions all through life.

c. carrier testing

d. prenatal testing (fetal testing)

e. predictive testing

Priya Should Find Out She Inherited a Fatal Disease (or should she?)

Priya has just lost her mother to an illness called Huntington’s disease. It was hard for Priya to watch her mother die. First her mother had strange changes of mood. Then her arms and legs began twitching. Soon she couldn’t talk or control her movements. In the end, she was totally bedridden and could barely get food down without choking. Priya knows that Huntington’s disease usually strikes people in middle age. It is always fatal, and there is no treatment. She also knows that since the disease is inherited, she has a strong chance of getting it herself. Priya just learned about a test she can take. The test will tell if she carries the gene for Huntington’s disease. She is tempted to take the test. She thinks that if she could find out once and for all whether she will get the disease, she could plan for her future. On the other hand, she wonders if it is better not knowing. At least then Priya would still have some hope. If you were Priya, what would you do?

<Huntington’s disease (HD)>

- Autosomal dominant.

o The probability of Priya inheriting the HD allele from her mother is 50 %.

- Develop in midlife.

- Persons with HD may show uncontrolled movement. They lose thinking ability and motor skill over the course of disease (10 – 20 years).

- No effective treatment available.

Predictive testing – Genetic testing of individuals showing no symptoms. Access the person’s risk of developing the disease.

Genetic counselling

- The result of genetic testing can be devastating.

- There is no way of predicting how you will react to positive or negative reactions.

- The test procedure and results should be explained thoroughly by professional advisors.

- Genetic counsellors help them clarify genetic testing and cope with the test results. They may suggest appropriate support (counsellor, support group, etc) to the individuals after the test.

Why do you think Priya wants to have her genetic testing long before her symptoms appear?

How do you think she would respond to the positive (i.e. she has the HD allele) or negative result (i.e. she does not have the HD allele)?

If she gets the positive result, who should she share the result? Her family? Her employer? Her insurance company?

If she gets the positive result, should she have children? There are different options for having children.

Carlos and Mollie Can Have a Perfectly Healthy Baby (or can they?)

Carlos and Mollie want to have children. However, they haven’t tried to start a family yet because they disagree on something important. Carlos wants Mollie to get tested to see if she is a carrier for cystic fibrosis (CF). Mollie doesn’t want to do it. People with CF have mutations in one or more genes. These mutated genes give faulty instructions for the production of proteins that help move salt in the body. One result is that the lungs become clogged with mucus, making it hard to breathe. Another result is that the body has a hard time digesting food. The disease can be painful and lead to an early death. Carlos had a brother with CF. He hated seeing his brother suffer so much. His parents struggled with the hardship and expense of caring for a sick child who never made it to adulthood. Carlos doesn’t want to repeat that experience in his own life. That’s why he had himself tested for CF. Unfortunately, he found out that he is a carrier. CF is a recessive disorder. That means his children will have the disease only if they inherit the mutated gene from both parents. Mollie can get tested to see if she carries the CF mutation. If she does, then when she gets pregnant they can have the fetus tested to make sure it does not have two CF genes and is therefore free of the disease. Mollie would prefer simply not knowing what the risks are. She figures that once a baby is in their arms, they will be glad they had it, no matter what. If you were Mollie or Carlos, what would you do?

- Autosomal recessive

o If both parents are carrier, the chance of their child getting CS is 25 %.

- Most common fatal genetic disorder

- Children with CS have difficulty breathing or digesting food.

- Vulnerable to infections

- The affected children may or may not make to the adulthood.

Carrier testing – Genetic testing to determine whether the person is a carrier of a

recessive genetic disorder.

If Mollie turns out to be a carrier of the CF allele, what are their options?

- They may decide not to get married.

- They may decide not to have children. They may want to adopt children instead.

- They may decide to have fetus tested while Mollie is pregnant (Prenatal testing).

- If the fetus has CF, they may decide to terminate pregnancy.

- They may consider in vitro fertilization. Sperms and eggs are fertilized in a petri dish. Obtained embryos can be tested for presence of the CF allele. The embryos that do not carry the CF allele are implanted to mother’s uterus. Very expensive procedure. High failure rate.

Even if they try everything to avoid a child with CF, they may still be end up with a sick child.

Even if they have a child with CF, advancement of medical research may provide him/her a better quality of life.

Howard’s Health Is Up to Him (or is it?)

Howard will turn 50 soon, and it worries him. His grandfather died of a heart attack in his fifties, and so did his father and uncle. Several years ago, a doctor told Howard that he was at high risk for heart disease because of his family history. But the doctor said that Howard could improve his chances if he lost some weight, stopped smoking, and exercised. The doctor also told Howard to come back every year for a checkup. Howard hasn’t gone on a diet, and he hasn’t given up his cigarettes or taken up exercise. He also hasn’t been back to the doctor. He’s afraid of what the doctor might find. Howard can’t make up his mind. Sometimes he thinks he should try to take better care of his health. Other times, he thinks that he should just accept the fact that he won’t live much longer and should get as much fun out of life while he can. If you were Howard, what would you do?