Genetics: Lecture 3 Flashcards
Mendelian Genetics & Pedigrees
Multiple Alleles?
Possibility of having one of 3, 4, 5 or more alleles on two homologous chromosomes for the same gene.
Co-dominance?
both can be present and are at once
Example: cows with white and brown spots
Lethal Alleles?
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
ABO Blood groups: Multiple allele system with co-dominance?
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.
Gene product of ABO group?
histo-blood group ABO system transferase (enzyme involved with transfers of carbohydrates specific to A or B but O have neither).
What is actually happening?
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.
Examples of lethal alleles?
Manx cats: short tail is desirable, two dominant (no tail) is lethal
Creeper chickens: Pp is desired form, PP is lethal
Human Karyotype?
A display of homologous chromosomes of a cell arranged by
size and type.
Giemsa Stain?
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!
Autosomes?
22 pairs of homologous chromosomes exactly the same in both male and female karyotypes.
Sex chromosomes?
One pair of chromosomes:
*Female XX
*Male XY
- in mammals
Multifactorial Disorders - Cancers?
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
Multifactorial Disorders - Congenital Malformations?
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
Multifactorial Disorders - Coronary Artery Disease?
Multiple causes, including genetic predisposition. Incidence: variable, but up to 1/15 in Western populations.
- common
Chromosome or Cytogenetic Disorder examples?
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
Nondisjunction?
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.
Nondisjunction gives rise to?
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)
Down syndrome?
- 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
Klinefelter syndrome?
An individual with 47 chromosomes, XXY. They are born sterile and male with female body characteristics.
- Trisomic
Turner syndrome?
An individual with 45 chromosomes, X. Born sterile and females with short stature and immature sex organs.
- Monosomic
XXX syndrome?
Individual with 47 chromosomes, XXX. Fertile woman associated with learning difficulties.
- typically goes undiagnosed
- trisomic
- associated with ADHD
XYY syndrome?
Individual with 47 chromosomes, XYY. Fertile male associated with behavioural difficulties.
- typically goes undiagnosed
- trisomic
- associated with ADHD
Single gene disorders?
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.
Cystic Fibrosis?
Cystic Fibrosis
* common autosomal recessive
disease
* Incidence: ~1/2000 in some
Caucasian populations
* very rare in Asians
Huntington’s disease?
Huntington’s Disease
* autosomal dominant, late onset.
* Incidence: variable 3/100000
* much higher in some small isolated
populations.
Duchenne Muscular Dystrophy?
Duchenne Muscular Dystrophy
* Common X-linked recessive
disorder.
* Incidence: ~1/3000-3500 males
* rare in females
Sickle Cell Anemia
Sickle Cell Anemia
* autosomal recessive.
* Incidence: common in equatorial
Africa
* ~1/400 African Americans affected
Three questions a clinical geneticist asks?
Is the genetic disorder:
- Autosomal or sex-linked?
- Dominant or Recessive trait?
- Caused by a single gene, or more than one gene?
Pedigree symbols? Male, Female, Sex unspecified.
Male - square
Female - circle
Sex unspecified - diamond
What does a pedigree help us see?
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.
Pedigree symbols? # of children of sex, affected, heterozygotes.
of children of indicated sex - symbol with a number on the middle
affected - symbol completely filled in
Heterozygotes for autosomal traits - half filled in
Pedigree symbols? Consanguineous mating and monozygotic twins. (less related)
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.
Pedigree symbols? Marriage, extramarital, divorce. (less related)
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
Albino pedigree. Autosomal or sex-linked?
If sex-linked the trait will be seen predominantly in males.
If autosomal then the trait will be seen more in females.
Albino pedigree. Dominant or recessive?
If dominant, every albino child will have an albino parent.
If recessive, not every albino will have an albino parent.
Albino pedigree. Single gene?
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
