Mendelian Inheritance

Mendelian Characteristics in Humans

15000+ pathological and non pathological characteristics

Recessive Trait

two copies of a particular allele are required for the phenotype to be seen

Dominant trait

only a single copy of the allele is required for the phenotype to be seen

Recessive X-Linked traits

in females, must have two copies of the allele for the trait to show; in males, since there is only one X-chromosome it must just have the one copy of the recessive allele

Pedigrees

similar to family trees but with information about the phenotype of individuals included

Autosomal dominant Inheritance

associated with a single gene on an autosome

Key features:

• affects either sex

• transmitted by either sex

• a child of an affected x unaffected mating has a 50% chance of being affected if affected parent is heterozygous

• an affected person usually has one affected parent

Huntington’s Disease

an autosomal dominant disease that is a neurological condition in which neurons controlling movement deteriorate; caused by a 3 nucleotide repeat in the huntingtin gene; number of repeats correlates with age of onset

Autosomal Recessive Inheritence

2 copies must be present for disorder to be present, located on autosomes

key features:

• affected people usually born to unaffected parents

• parents of affected people are usually asymptomatic carriers

• increased incidence with parental consanguinity

• affects either sex

• transmitted by either sex

• two carrier parents have 25% chance of having affected offspring

Cystic Fibrosis

Autosomal Recessive Disease that affects the lungs and digestive tract; caused by mutation in transmembrane chlorine transporter leading to a build up of mucus that clogs the lungs

X-Linked Recessive inheritance

2 copies of mutant allele must be present for allele to be expressed, but since males only have one allele, having only one copy will cause diseases; females typically are unknowing carriers

key features

• affects mainly males

• affected males are usually born to unaffected parents, mother usually being a carrier

• affected females can be born to affected fathers and carrier mother , or may occur due to non-random X-inactivation

• no male to male transmission!

Hemophilia

a X-linked recessive disorder that results in the inability to control blood clotting and coagulation; very common in European royal families

X-linked dominant Inheritance

Key features

• affects either sex, but more females

• females are often more mildly or variably affected than males

• the child of an affected female has a 50% chance of being affected regardless of gender

• the child of an affected male has a 100% chance of being affected if its a girl an 0% chance of being affected if its a boy

Y-linked dominant

No disorders are currently known to be Y linked

Key Features

• affects ONLY males

• affected males would always have an affected father

• all sons of affected men are infected

Complications of basic pedigree patterns

common recessive traits, mitochondrial inheritance, genetic imprinting, X-linked dominant male lethality, non penetrance of dominant traits, novel mutations

Common Recessive traits

if a character is common in a population, there is a high chance of it being brought into the pedigree independently by two or more people producing a pattern resembling dominant inheritance

mitochondrial inheritance

mitochondrial mutations are a significant cause of human disease, mitochondrial diseases have a matriarchal line of inheritance; can affect both sexes but can only be passed down from mother

Genetic Imprinting

parent-of origin specific epigenetic modifications sometimes lead to exclusive expression of genes from only one parent; often characterized by passage down a parental line and/or skipping of generations

X-linked dominant male lethality

for some X-linked dominant conditions absence of normal allele is lethal before birth; affected males are not born so condition is only seen affecting females; affected females pass this on to half their daughters and none of their sons

Incontenia Pigmenti

An X-linked dominant disease that is lethal to dominant males; leads to discolored skin caused by excessive deposits of melanin; mutation in IKBKG gene

Non-penetrance of autosomal dominant traits

non penetrance means the person has the genotype but does not manifest the phenotype, so it appears that they have the recessive trait

novel mutations

people with these severe genetic disorders rarely reproduce and pass on their mutations; when a child with no family history shows severe abnormalities it is difficult to decode the mode of inheritance

multifactorial inheritance patterns

many diseases are not caused by a single gene, but an interplay of genetic factors and environmental factors; genetics can predispose you to certain diseases but not cause them, this is much more difficult to trace through pedigrees