Inheritance: Nuclear & Mitochondrial DNA Flashcards

Flashcards about Inheritance: Nuclear & Mitochondrial DNA

ALLELES

Alternative versions of a gene at a given locus.

Allele Notation in Pedigrees

In pedigrees, alleles are usually denoted by upper- and lower-case versions of the same letter, i.e.: AA, Aa, aa.

UPPER-CASE Letter in Allele Notation

Usually denotes the DOMINANT allele (A).

SMALL-CASE Letter in Allele Notation

Usually denotes the RECESSIVE allele (a).

HOMOZYGOUS

A person with both alleles identical at a given locus.

HETEROZYGOUS

Different alleles at a given locus.

HEMIZYGOUS

Only a single allele possible at a given locus.

HETEROPLASMIC

When only a single allele is possible at a given locus BUT the individual still shows two alleles.

Autosomal Dominant

Manifests in the heterozygous.

Autosomal Recessive

It doesn’t show in the heterozygous.

Males and X-linked characters

Males (♂) are HEMIZYGOUS for any character associated with X so no recessive characters possible for ♂

Autosomal Dominant Characteristics

An AFFECTED INDIVIDUAL usually has AT LEAST one affected parent, affects either sexes, and is transmitted by either sexes. A child with one affected (heterozygous) and one unaffected parent has 50% chance of being affected.

Examples of Autosomal Dominant Conditions

Achondroplasia, Huntington’s disease, most blood group genes.

Examples of Autosomal Dominant Conditions with Late Onset

Familial Breast Cancer, Huntington’s disease, Alzheimer’s disease.

Autosomal Recessive Characteristics

An affected individual is usually born to UNAFFECTED PARENTS (usually asymptomatic carries), increased incidence in case of consanguineous couples, affects either sexes, and is transmitted by either sexes. After the birth of an affected child, each subsequent child has 25% chance of being affected.

Examples of Autosomal Recessive Conditions

Cystic fibrosis, Tay-Sachs.

X-linked Recessive Characteristics

It AFFECTS MAINLY MALES. Affected males are usually born to UNAFFECTED PARENTS, there is NO MALE TO MALE TRANSMISSION in the pedigree.

Examples of X-linked Recessive Conditions

hemophilia A & hemophilia B, Duchenne muscular dystrophy.

X-linked Dominant Characteristics

It affects either sexes, but MORE FEMALES than males, usually at least one parent is affected, females are often more mildly and more variably affected. If affected male → ALL HIS DAUGHTERS but NONE OF HIS SONS are affected.

Examples of X-linked Dominant Conditions

Congenital Hemidysplasia with Icthyosiform erythroderma and Limb Defects (CHILD syndrome), Fragile X syndrome.

X-inactivation (LYONIZATION)

A process that occurs early in the embryo development (~8- cell stage).

X-Chromosome Inactivation and Mosaicism

An heterozygous female is a MOSAIC OF CLONES in which alternative alleles are expressed.

Y-linked Conditions Examples

Hypertrichosis PINNAE Auris (Hairy ears), Spermatogenic failure.

Y-linked Inheritance Characteristics

Y-linked diseases/anomalies are rare, affect only males (with some exceptions), affected males always have an affected father (unless there is a new mutation), all sons of an affected father are affected.

Mitochondrial Genome Normal Functions

Mitochondrial oxidative phosphorylation (OXPHOS) makes ATP energy production.

Mitochondrial dysfunction inheritance

Mitochondrial DNA depletion Syndrome 8a (MTDPS8A), Isolated mitochondrial myopathy (IMMD), HSD10 mitochondrial disease (HSD10MD), Combined oxidative phosphorylation deficiency-6 (COXPD6), Leber hereditary optic neuropathy (LHON).

Mitochondrial DNA (mtDNA) Characteristics

Maternal inheritance, high number copies per cell, much higher mutation rate than nuclear DNA (nDNA), mitochondrial diseases caused by mtDNA mutations AFFECT BOTH SEXES, never transmitted by a father to his children, there are highly variable clinical manifestations often due to HETEROPLASMY.

Mitochondrial DNA Inheritance Examples

Myopathy, Encephalopathy, Lactic Acidosis, Stroke-like Episodes (MELAS), Leber Hereditary Optic Neuropathy (LHON).

Complexity in Single Gene Disorders

Unusual features in single-gene patterns of inheritance can be explained by phenomena such as MOSAICISM, MITOCHONDRIAL INHERITANCE, Genetic heterogeneity, Anticipation, Imprinting, and Uniparental disomy.

Genetic Heterogeneity

A disorder (same phenotype) can be caused by more than one genetic mechanism (Retinitis pigmentosa, Charcot-Marie-Tooth disease, Ehlers-Danlos syndrome).

Anticipation

Either the onset of the disease occurs at an earlier age in the offspring than in the parents or the disease occurs with increasing severity in subsequent generations.

Examples of Anticipation

Myotonic dystrophy, Fragile X-syndrome, Huntington disease.

Genomic Imprinting

“Parent of origin effect” where genes on homologous chromosomes are expressed differently if inherited from the father or the mother. Due to DNA methylation mostly occurring at CpG site.

Examples of Genomic Imprinting

Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS).

Uniparental Disomy (UPD)

Both homologues chromosome pair inherited from one parent.