Monogenic traits Flashcards
Define monogenic traits
Due to differences in product of single genes. Discrete rather than quantitative traits. they are special cases
How do gene variants arise (mutations)
Mutation is the process by which genes change from one allelic form to another. Creation of new alleles can occur.
Mutate randomly at any time and in any cell.
Can occur during normal replication and not be repaired.
mutations carried by gametes can be transmitted from parents to offspring.
What are the three types of mutation at DNA nucleotide level
Substitutions, insertions, deletions
many have no consequences for the ind.’s phenotype
what is loss of function?
many places in a gene where a mutation can knock out function
gain of function?
occasionally a mutation may alter the gene product, in particular its shape. conformational and other changes may lead to changes in function
what are mutant and wild type alleles
The most common phenotype in a natural population defines the wild type allele.
Rare alleles, less than 1% freq, are mutant alleles.
Dominant allele?
Recessive allele?
When present, always expressed or seen.
recessive - only expressed/seen when it is the only allele present
How are wrinkles and other trait variants produced?
Allele R is dominant. functional enzyme that leads to conversion of unbranched to branched starch. -> round phenotype.
both recessive alleles leads to inactive enzyme so starch remains unbranched. -> wrinkled phenotype.
What about long and short stems?
Dominant L allele leads to functional gibberellin 20 oxidase, so gibberellin is activated by the enzyme, leading to long stems.
recessive l allles however, inactive gibberellin 20 oxidase, to inactive gibberellin. - short stems
Loss of function mutations and recessive traits
Loss of function mutations often cause recessive traits.
i.e. only matters whether protein is present at all. e.g. WT phenotype of homozygotes and heteroxygeotes ++ or +m given by presence of protein, but not sensitive to quantity.
presence of mutant allele does not alter the phenotype for the +m compared with ++.
But, loss of function mutations can cause dominant traits
This is the case when phenotype is sensitive to quantity of protein and therefore the disease allele would be dominant.
e.g. the gene encoding type I collagen, structural protein required in large amounts to make the bone. loss of function mutant causes brittle bone disease. therefore disease allele is dominant because the phenotype is sensitive to the quantity of protein.
Gain of function mutations are rare and likely to be dominant. Please explain
Presence of any of the mutant protein affects expression of the phenotype. e.g. +m and mm show mutant phenotype. the WT allele is recessive in gain of function mutations.
but… gain of function mutation can also cause recessive traits
Explain how sickle cell anaemia is a recessive trait
E.g. sickle cell anemia is a recessive trait. Allele 1 - Hba normal haemoglobin. Allele 2 - HbS - sickle cell haemoglobin.
sickle cell haemoglobin HbS polymerises when oxygen is released, deforming the RBCs. This is a gain of function compared to HbA. After repeated cycles, the HbS RBCs membranes become rigid and lose the biconcave shape of normal haemoglobin. Circulation through capillaries is blocked, causing tissue hypoxia, pain and organ damage.
Sickle cell disease only occurs in HbS homozygotes. Therefore, disease phenotype is recessive.
At the same time, resistance to malaria is not a recessive trait. explain why?
HbS heterzygotes care called sickle cell trait and individuals are healthy.
There is another phenotype.
HbS heterozygotes living in malarial regions are greatly protected from malarial disease, due to propensity of HbS to sickle. So for this phenotype, HbS allele (the same allele mind you) is not recessive.
This example shows that same element can be looked at from different perspectives i.e. what specific phenotype are we looking at?
Why can it be more complex than monogenic traits?
list 5 things.
A gene may have >2 alleles. Dominance is not always complete. One gene may contribute to several visible characteristics Some alleles may cause lethality Variable penetrance
ABO blood groups. List the three alleles and phenotypes.
IA IB and i
each ind. will carry two alleles there are four different phenotypes IAIA, IAI IBIB, IBI IA, IB ii
What are the two ways in which dominance may be incomplete?
Co-dominance - F1 hybrid may resemble both parents - alternative traits are both visible.
Incomplete dominance - F1 hybrid resembles neither pure bred parent. e.g. crossing red and white snapdragons leads to pink hybrid progeny. because one copy of the red producing enzyme alllee leads to only enough pigment to make flowers look pink . White results when there is no functional enzyme.
What is pleiotrophy and describe an example
It is multiple phenotypes - possible distinct and seemingly unrelated, due to allelic variation in a single gene.
Nail-patella syndrome
single gene affects thumbnails and kneecaps along with other phenotypes such as glaucoma, so ind. present complex phenotype.
syndrome traces back to a protein (encoded by a single gene) that carries out actions affecting the expression of many other genes.
Autosomal dominant inheritance.
Some alleles may cause lethality.
A coat colour variant can be lethal. inheritance of a recessive lethal allele that also produces a dominant coat colour phenotype.
AY AY homozygotes do not survive.
Phenotypes with variable penetrance. Siamese cats example
Siamese cats homozygous for a particular allelic variant of a gene that encodes an enzyme for catalysing melanin
enzyme variant is temperature sensitive
does not function at cats normal body temperature, only at cooler body extremities. hence variation in the colour o the cat
Cystic fibrosis - how complex a monogenic trait can be
Trait caused by a single gene called CFTR gene on chromosome 7. the regulator protein CFTR is involved in production of sweat, digestive fluids, and mucus. CFTR, when not functional, secretions become thicker.
Pleiotophy - lung abnormal mucus - chest infection, lung damage
sweat glands, elevated chloride, sodium in sweat, gastrointestinal tract, pancreas, reproductive teact
recessive trait, both copies of gene to have trait.
there are multiple alleles. Most common mutation is a deletion mutation called delta F508 in the CFTR gene. Abnormal channel breaks down, never reaches the cell membrane to transport chloride ions.
Variable penetrance - features of disorder and severity varies among individuals depending on combination of mutations on the two copies of the gene.
The point of this lecture
Dominant / recessive describbe observation on transmission of trait variants - terms only make sense of the inheritance of specified traits.
monogenic traits are a subset of all possible genotype-phenotype relationships . the simplest one to understand.
relationships better understood by studying functions of genes
dominance/ recessive characteristics do not describe any aspect of functional or biological quality.
