Genetic 2.2: Autosomal Dominant Flashcards
True or False,
Transmission autosomique dominante cannot have a Transmission homme à homme
False,
Transmission homme à homme possible
What can be said of the parents of someone who has an autosomique dominante?
One of the parents will also be affected by autosomique dominante.
Individus atteints dans chaque génération
achondroplasie -> personnes de petites tailles. What type of disease?
Transmission autosomique dominante
2 parents atteints ont 25% risque de
transmettre forme homozygote: sévère létale
What is Pénétrance? What example should remiond us of this?
Fréquence avec laquelle un génotype donné produit ses effets sur le phénotype
Ectrodactylie: Split-hand deformity
Probability of a affected genotype to show a phenotype (in domiant autosomal mutations)
Example, dominant disease, granpa has it, dad doesnt but child does…What happened?
Saute de generation
What is Expressivité?
The same mutation on the same gene can lead to different phenotypes
We talked about cystic fibrosis and how it can cause pneumonary issues but in other patients cause infertility (althouhg this is recessive and we are tlaking abt dominant here)
A better example.
polydactylie. Some patients have only one hand, some have both hands and legs etc
What is Syndrome de Marfan?
Syndrome à transmission autosomique dominante
Pénétrance complète
BUT: Expressivité variable intra-familiale et inter-familiale
Combinaison de facteurs génétiques et environnementaux qui influencent
l’effet de la mutation. Either factors that reduce or increase risk.
What is Neurofibromatose?
Penetrance avec age
Transmission autosomique dominante
Expressivité variable
However, more often than not the parents are usually not AFFECTED!!!!
mutations de novo;
Say you have a child with a autosomique dominant mutation but both his parents are not affected. What explains this?
Potential mutations de novo
(could have to do with penetrance or variable expressivity but if we knew more about the disease then we would be certain to say de novo)
Given a family who had a child with a dominant mutation de novo, what are the chances that they have another one?
Depends on masaicism or not
If the parents are mosaic and have a mutation in their gonadic cell line, the chances are high
However, most likely it was just a de novo and so the chances are 1%
What is a Mutation de novo?
A mutation that is not seen as a phenotype or genotype in the parent but is present in the child
What could we infer if we have a dominant “de novo” mutation that is commune aux 2 enfants if the parents are both tested negative for the mutation?
Mosaïcisme germinal!!! Chances for a child to have the disease up to 50%
The germinal cell line of the mother or father has the mutation althiugh the dad doesnt
What is an innactivationg bias?
Femmes ont deux copies de ces gènes
* Inactivation du chromosome X pour que le dosage génique soit équivalent à l’homme
Phénomène aléatoire Xp vs Xm
Inactivation biaisée: inactivation préférentielle vers un des chromosomes X
There can be certain signals that will bias choosing one X over the other. Example when one has a bad mutation.
This is sorta like mosaicism.
Hérédité liée à l’X récessif
rules of thumb
La mutation s’exprime chez tous les garçons qui la portent
femmes hétérozygotes ne manifestent habituellement pas les signes typiques
Peuvent manifester des signes si inactivation du X biaisée (rare)
** Toutes les filles d’un homme atteint seront automatiquement porteuses (100%)**
Aucune transmission d’homme à homme observée (0%)
Because he gives the healthy Y
La règle de Haldane
A. For a chromosome X disease that is lethal in guys (or reduces their reproductive potential)
1. if the disease continues to exist in a population
2. the risk of de novo mutations is 1/3
3. The risk of the mother being a carrier is 2/3
There is no way for the father to have transmitted due to A.
Disease Lié à l’X récessif (2)
dystrophie musculaire de Duchenne
(majorly deNovo due to decreased reproductive fitness)
hemophilie A
a woman can have homologous mutations
