Genetics: Lecture 3

Question 1

Multiple Alleles?

Answer 1

Possibility of having one of 3, 4, 5 or more alleles on two homologous chromosomes for the same gene.

Question 2

Co-dominance?

Answer 2

both can be present and are at once

Example: cows with white and brown spots

Question 3

Lethal Alleles?

Answer 3

Allele whose presence will lead to death. Typically won’t produce offspring if one is homozygous.

Ratio of offspring is not 3:1 but 2:1

Question 4

ABO Blood groups: Multiple allele system with co-dominance?

Answer 4

There are three alleles for the ABO blood groups and their carbohydrates.

Multiple alleles because options are A, B and O

Co-dominance because they work together when having AB and AO etc.

Question 5

Gene product of ABO group?

Answer 5

histo-blood group ABO system transferase (enzyme involved with transfers of carbohydrates specific to A or B but O have neither).

Question 6

What is actually happening?

Answer 6

The A allele produces the enzyme A-transferase which catalyzes the transfer of GalNAc residues.

The B allele encodes the enzyme B-transferase, which catalyzes the transfer of galactose residues wikipedia

The i allele lacks both enzymatic activities

• antigens and antibodies are produced in each case which impact the compatibility.

Question 7

Examples of lethal alleles?

Answer 7

Manx cats: short tail is desirable, two dominant (no tail) is lethal

Creeper chickens: Pp is desired form, PP is lethal

Question 8

Human Karyotype?

Answer 8

A display of homologous chromosomes of a cell arranged by
size and type.

Question 9

Giemsa Stain?

Answer 9

Giemsa stain band ≠ gene !

Giemsa stain is just a nucleic acid stain that attaches preferentially to adenine-thymine (A-T) bonds.

There are way more genes on a chromosome than there are Giemsa stain bands

Example: HUMAN CHROMOSOME 22 has 49 Million base pairs and between 417 - 496 genes!

Question 10

Autosomes?

Answer 10

22 pairs of homologous chromosomes exactly the same in both male and female karyotypes.

Question 11

Sex chromosomes?

Answer 11

One pair of chromosomes:
*Female XX
*Male XY

• in mammals

Question 12

Multifactorial Disorders - Cancers?

Answer 12

Some forms; multiple causes, including genetic predisposition. Incidence: >1/3 (exclusive of skin cancer).

• very common
• genetic predisposition
• closer to 1/2 including skin cancer

Question 12

Multifactorial Disorders - Congenital Malformations?

Answer 12

Cleft lip, heart defects, neural tube defects. Incidence: variable but
generally 1/250-600 with ethnic variation.

• varies by population and somewhat common
• congenital malformations are those that someone is born with

Question 13

Multifactorial Disorders - Coronary Artery Disease?

Answer 13

Multiple causes, including genetic predisposition. Incidence: variable, but up to 1/15 in Western populations.

• common

Question 14

Chromosome or Cytogenetic Disorder examples?

Answer 14

Down syndrome/ trisomy 21: incidence is 1/800
- Highly associated with the age of the mother at fertilization.

XYY Syndrome/ extra Y: incidence is around 1/1000 males

Question 15

Nondisjunction?

Answer 15

Occurs during meiosis, causes trisomies and monosomies.

• occurs when chromosomes (sister chromatids or homologs) are pulled to the wrong side in meiosis I or II. We want an even split of the genetic material and nondisjunction means that that cannot occur.

Question 16

Nondisjunction gives rise to?

Answer 16

Monosomics
- Lack a single copy of a chromosome (monosomy).
- Rare, typically lethal
- Happens with single X chromosomes

Trisomics
- Carry an additional copy of a chromosome (trisomy).
- Trisomy 21 is the most common (only viable)

Question 17

Down syndrome?

Answer 17

• Trisomy 21, an additional chromosome 21 in the karyotype,
  owing to nondisjunction during
  meiosis.
• Portion of chromosome 21 translocated to chromosome 14
• Incidence of Down Syndrome (and other trisomies) increases dramatically with the age of the mother

Question 18

Klinefelter syndrome?

Answer 18

An individual with 47 chromosomes, XXY. They are born sterile and male with female body characteristics.

• Trisomic

Question 19

Turner syndrome?

Answer 19

An individual with 45 chromosomes, X. Born sterile and females with short stature and immature sex organs.

• Monosomic

Question 20

XXX syndrome?

Answer 20

Individual with 47 chromosomes, XXX. Fertile woman associated with learning difficulties.

• typically goes undiagnosed
• trisomic
• associated with ADHD

Question 21

XYY syndrome?

Answer 21

Individual with 47 chromosomes, XYY. Fertile male associated with behavioural difficulties.

• typically goes undiagnosed
• trisomic
• associated with ADHD

Question 22

Single gene disorders?

Answer 22

Caused by a mutant gene allele.
- The mutant allele may be present on only one chromosome of an homologous pair (dominant) or on
both chromosomes (recessive) to exhibit the disease.

Usually obvious pattern of inheritance in a pedigree.
- Most defects are rare.

Question 23

Cystic Fibrosis?

Answer 23

Cystic Fibrosis
* common autosomal recessive
disease
* Incidence: ~1/2000 in some
Caucasian populations
* very rare in Asians

Question 24

Huntington’s disease?

Answer 24

Huntington’s Disease
* autosomal dominant, late onset.
* Incidence: variable 3/100000
* much higher in some small isolated
populations.

Question 25

Duchenne Muscular Dystrophy?

Answer 25

Duchenne Muscular Dystrophy
* Common X-linked recessive
disorder.
* Incidence: ~1/3000-3500 males
* rare in females

Question 26

Sickle Cell Anemia

Answer 26

Sickle Cell Anemia
* autosomal recessive.
* Incidence: common in equatorial
Africa
* ~1/400 African Americans affected

Question 27

Three questions a clinical geneticist asks?

Answer 27

Is the genetic disorder:

1. Autosomal or sex-linked?
2. Dominant or Recessive trait?
3. Caused by a single gene, or more than one gene?

Question 28

Pedigree symbols? Male, Female, Sex unspecified.

Answer 28

Male - square
Female - circle
Sex unspecified - diamond

Question 28

What does a pedigree help us see?

Answer 28

Looking at a pedigree gives us the representation of the family tree regarding that specific gene and how it is moved through generations. Then we can make inferences and answer the 3 questions.

Question 29

Pedigree symbols? # of children of sex, affected, heterozygotes.

Answer 29

of children of indicated sex - symbol with a number on the middle

affected - symbol completely filled in

Heterozygotes for autosomal traits - half filled in

Question 30

Pedigree symbols? Consanguineous mating and monozygotic twins. (less related)

Answer 30

Consanguineous mating - square connected to circle with two lines

Monozygotic twins - half square and square connected in side and at the top into a point.

Question 31

Pedigree symbols? Marriage, extramarital, divorce. (less related)

Answer 31

Marriage - single line connecting square and circle

Extramarital mating - square and circle attached by a dotted line

Divorce - square and circle attached with a line stuck through the line

Question 32

Albino pedigree. Autosomal or sex-linked?

Answer 32

If sex-linked the trait will be seen predominantly in males.

If autosomal then the trait will be seen more in females.

Question 33

Albino pedigree. Dominant or recessive?

Answer 33

If dominant, every albino child will have an albino parent.

If recessive, not every albino will have an albino parent.

Question 34

Albino pedigree. Single gene?

Answer 34

If a single gene, then albinos born to heterozygous parents should occur in families at a frequency of approximately 25%. Therefore we look at the heterozygous parents (affected children present but not affected parents).

• this prediction is due to using a Punnett square