Génétique Mendélienne: Cours M6

M6 – Génétique: Actualisation Fiche de cours n°3

• This document is a genetics course update, focusing on Mendelian inheritance.

Rappel (Reminder)

• The basis was defined by Gregor Mendel through his work on pea plants.
• Mendel's particulate inheritance laws were established in 1866.
• Confirmation of these laws came from the work of de Vries et al. in 1900.

Transmission Mendélienne - Parents

• Parents: Purebred plants with smooth, yellow seeds crossed with plants having wrinkled, green seeds.
• First Generation: All seeds were smooth and yellow.
• Subsequent Generations: Four possible phenotypes emerged.
• 9/16: Smooth and yellow seeds
• 3/16: Smooth and green seeds
• 3/16: Wrinkled and yellow seeds
• 1/16: Wrinkled and green seeds

Lois de Mendel - Lois

• Mendel's experiments started with two pure lines of pea plants: green phenotype crossed with yellow phenotype.
• First Law of Mendel (Law of Uniformity): The hybrids in the F1 generation are identical.
• All F1 generation pea plants are the same color (yellow).
• 75% of F2 pea plants have the same color (yellow).
• 25% of F2 pea plants have a different color (green).

Interprétations des Resultats (Interpretations of Results) - Dominance

• Yellow is the dominant color, represented by allele J.
• Green is the recessive color, represented by allele v.
• All F1 generation pea plants exhibit the dominant color
• Homozygosity/Heterozygosity:
• Parents from pure lines are homozygous

2ème LOI DE MENDEL - Lois

• 2nd Law of Mendel (Law of Segregation): Character segregation in gametes.
• 75% of F2 generation pea plants have the dominant color.
• 50% are homozygous (JJ)
• 25% are heterozygous (Jv).
• 25% of F2 generation pea plants have the recessive color.
• All are homozygous (vv).

Faire un Arbre Généalogique - Généalogie

• Guide to constructing a pedigree chart with international symbols.
• Subjects: Symbols for male, female, and unknown sex.
• Unions: Symbols for unions between unrelated individuals, consanguineous unions, couples without children, and infertility.
• Children: Symbols for a sibship, with children represented in birth order, and indication of pregnancy.
• Generations: Representation of different generations.
• Twins: Symbols for dizygotic and monozygotic twins.
• Persons affected by a disease, and if the phenotype variable.
• Disease linked to the X chromosome.
• Consultation and Propositus.
• Spontaneous Abortion.

Modes de Transmission - Transmission Autosomique Dominante

• Autosomal Dominant Transmission
• Pathological Allele: A is responsible and located on an autosome.
• It is dominant over the normal allele (a).
• Expression: Manifests in heterozygotes (Aa) and homozygotes (AA).
• Homozygous (AA) humans are rare.
• Affects both sexes
• Transmission: Occurs through both sexes.
• Risk: 1 in 200 chance of occurrence.
• Exceptions:
• Neomutation
• Variable Expressivity
• Incomplete Penetrance
• Anticipation
• Co-dominance and semi-dominance

Autosomal Dominant Transmissions - Neomutations

• Neomutation
• Absent in parent's genome
• Mutation transmited through egg cells
• Expressivité Variable
• Clinical presentation varies in individuals
• Cases are frequent
• Phenotypes vary based on disease symptoms

Transmission autosomique dominante - Neuro

• Example: Neurofibromatosis Type 1
• Clinical Signs: High variability including malignant tumors, café au lait spots, neurofibromas, and Lisch nodules.
• This genetic disease is frequently caused by mutation of the NF1 gene.
• The NF1 gene codes for neurofibromin, a tumour suppressant protein
• 50% of cases are due to neomutations.

TRANSMISSION AUTOSOMIQUE DOMINANTE - Penetrance

• Penetrance
• Complete: 100% of mutation persons that are affected
• Incomplete: Some mutation carriers are not affected
• Example with the dystonie myoclonique

Transmission autosomique dominante - Anticipation

• Anticipation Definition: A mechanism causing increased disease severity or earlier onset across generations.
• Mutations: Changes across generations, like triplet repeats.
• Huntington's Chorea: Based on triplet repeats

Co-dominance et Semi-dominance - Lois

• Co-dominance and Semi-dominance
• Co-dominance: When two phenotypic traits are expressed simultaneously.
• Example: ABO blood group system where A and B are co-dominant.
• Semi-dominance: The resulting phenotype expresses both alleles in intermideate.

TRANSMISSION AUTOSOMIQUE RECESSIVE - Modes

• Autosomal recessive transmission.
• The allele for disease (a) is located on an autosome. It is recessive to the normal allele (A).
• The disease only expresses in homozygotes (aa).
• The condition affects both sexes and is transmitted by both sexes.
• Parents must be healthy heterozygotes (Aa). Transmition a 1/4 risk.
• The affected subject has a low risk of having an affected child if the other parent is generally not a carrier.

Transmission autosomique dominante - Fréquences

• Exceptions to the Rules:
• The risk depends on the frequency of heterozygotes in the general population.
• Consanguinity
• Increased risk if parents is closely related
• Héterozygotes composites
• Different pathogenic allele on a nivel molecular

TRANSMISSION AUTOSOMIQUE RECESSIVE - Examples

• Conditions:
• Anémie à cellules falciformes
• Drépanocytose
• Mucoviscidose

TRANSMISSION LIEE AU CHROMOSOME X - Transmission

• Transmission Recessive Linked to X
• Affects hemizygous males and heterozygous females
• Heterozygous women are conductors
• There is 50% of have sons affected and there is 50% women is conductor.

TRANSMISSION LIEE AU CHROMOSOME X - Transmission

• Transmission Dominante Linked to X
• Parents porteurs de l'Xa malades
• Transmited trough aux deux sexes
• There is 1/2 risk to have a enfant atttaint

TRANSMISSION LIEE AU CHROMOSOME X - Létalité

• TRANSMISSION SEMI-DOMINANTE LIEE A I'X
• Symptom is less marked in women and men.
• TRANSMISSION DOMINANTE LIEE A I'X
• LÉTALITÉ DE L'HÉMIZYGOTE MALADE
• Létalité during the grossese

TRANSMISSION LIEE AU CHROMOSOME X - Syndrome

• TRANSMISSION LIEE AU CHROMOSOME X
• SYNDROME DE L'X FRAGILE
• Anomalie FRAXA qui touche le bras long du chromosome X et concerne le gène FMR1.

TRANSMISSION LIEE AU CHROMOSOME Y - Holandrique

• Transmission Linked to the Y Chromosome
• Holandrique Heredity
• Heredity affects the chromosome Y

HETEROGENEITE / HOMOGENEITE GENETIQUE - Definition

• HETEROGENEITE / HOMOGENEITE GENETIQUE
• Affections homogènes
• Affections génétiquement hétérogènes

UN GENE : PLUSIEURS MALADIES - Definitions

• UN GENE: PLUSIEURS MALADIES
• Le FGF interagit avec sont récepteur FGFR3 pour déclencher la différenciation et la croissance osseuse.
• Mutations can cause a different disease.
• Achondroplasie:
• Hypochondroplasie.
• Nanisme thanatophore.

DOMINANCE ET RECESSIVITE

• Dominance and Recessivity
• It is the mutation that determines the mode of transmission.
• For many genes, one can have dominant or recessive diseases
• Example
• Fibrinogénémie
• Hypercalcémie hypocalciurique

PENETRANCE ET EXPRESSIVITE VARIABLE - Description

• Definition of Penetrance and expressivité.
• variabilité of signs
• Si chiffre < 1 alors pénétrance incomplète.
• Example to expressivité variable

PENETRANCE ET EXPRESSIVITE VARIABLE - Tentatives

• PENETRANCE ET EXPRESSIVITE VARIABLE
• TENTATIVES D'EXPLICATIONS
• Facteurs d'environnement
• Gènes modificateurs
• Allèles modificateurs
• Empreinte parentale

PENETRANCE ET EXPRESSIVITE VARIABLE - Mosaïques

• MOSAÏQUES
• Simulent un défaut de pénétrance