Pattern of Inheritance

Question 1

What are the genotype and phenotype?

Answer 1

Genotype is which alleles are present at a locus, the allele that determines phenotype (observed traits) is dominant. Penetrance relates to phenotype because it’s the carriers that exhibit the phenotype.

Question 2

What are 8 factors that affect expression of inheritance?

Answer 2

• New mutations (de novo) = risk of increase with paternal age because mitotic divisions, also usually autosomal dominant.
• Germline mosaicism = mutation during embryotic development that affects all or part of parent germline.
• Reduce penetrance = individual with genotype, but no phenotype.
• Age-dependent penetrance = not apparent until later on (exp. Huntington’s Disease & Alzheimer’s).
• Variable expression = degree of severity is a range where in penetrance it is all or nothing.
• Allelic heterogeneity = phenotype caused by multiple mutations of the same gene.
• Locus heterogeneity = same disease caused by different loci.
• Pleiotropy = single gene mutation with multiple effects.

Question 3

What 4 factors affect severity of mutation?

Answer 3

• Incomplete dominance = homozygous (usually have more severe conditions).
• Manifest heterozygote = heterozygotes for recessive (usually mild).
• Sex-influenced dominance = some traits dominant in one gender.
• Pseudodominant = recessive homozygote (mating appears like dominant transmission).

Question 4

What are properties of autosomal dominant disorders?

Answer 4

Need one heterozygote, has vertical transmission (doesn’t skip generation), lots of times can be due to new mutations with paternal age. another example is familial hypercholesterolemia which is usually more lifestyle, but when autosomal, it is caused by LDL-receptor deficiency. This disease shows incomplete dominance because some have LDL-receptors.

Question 5

What’s two hit theory with carcinogenesis?

Answer 5

We can see in the case of retinoblastoma gene. One can inherit mutated gene and be okay (one hit), but if other gene is mutated (new) the individual develops the tumor (second hit). Non hereditary could be if person developed 2 new mutations of same gene (unlucky). Other autosomal cancers: Li Fraumeni, Neurofibromatosis, Breat/Ovarian Cancer, Lynch Syndrome

Question 6

What’s neurofibromatosis?

Answer 6

Shows variable expression where patients can have cafe au lait spots or neurofibromas; person who’s mild can have child who’s severe.

Question 7

What’s achondroplasia?

Answer 7

Dwarfism; heterozygotes 100% penetrant (usually caused by new mutations), homozygotes die

Question 8

What causes Marfan’s?

Answer 8

Mutation in fibrillin, has many different mutations (heterogeneity) and variable expression, also pleiotropic because affects ocular, skeletal, and cardiovascular.

Question 9

What’s cystic fibrosis?

Answer 9

Autosomal recessive disease that usually affects white people(population stratification) and causes mutation of CFTR gene which is chloride channel. Has allelic heterogeneity because has many mutations, can have any mutation with F508 (compound), and pleiotropic and variable expression leads to sterility, lots of sweat, diabetes, pancreatic disfunction.

Question 10

What are enzymatic or metabolic disorders usually caused by?

Answer 10

Autosomal recessive disorders, for example alkaptonuria and lysosome storage disease.

Question 11

What are properties of x-linked recessive disorders?

Answer 11

They usually affect males so no father-son transmission. Some diseases are hemophilia, mutations in coagulation factor 8, and allelic heterogeneity. Another exp. is Duchene’s. This is muscle weakness and the disease is still around due to females being heterozygous which allows for new mutations.

Question 12

What are x-linked dominant disorders?

Answer 12

There is no father-son transmission, all daughters are affected. An example is Rett Syndrome which is autistic-like behavior.

Question 13

What are two sex-linked disorders?

Answer 13

Pattern baldness which affects mostly males and is a mutation in their androgen receptor. Another example is a Y-chromosome mutation which leads to infertility.

Question 14

What is an example of codominance?

Answer 14

In blood, AB express both antigens. Also, in epistasis a person can have a genotype IA or IB but, the Bombay gene, if homozygous recessive, will mask IA or IB and give the individual O-Blood type.

Question 15

What’s mitochondrial inheritance?

Answer 15

Some traits tend to cluster in families, but are not transmitted in a Mendelian fashion. Ex. Congenital anomalies: Cleft lip and palate Spina bifida Pyloric stenosis

Question 16

Polygenetic inheritance

Answer 16

Quantitative traits like height and blood pressure are caused by the additive effects of multiple genes, with little or no environmental influence. We express quantitative traits when a number of genetic and environmental liability factors push us pass threshold = threshold model

Question 17

What’s an example of multifactorial risk?

Answer 17

Pyloric stenosis = Hyperplasia of muscles of the pyloris of the stomach causes obstruction of gastric emptying; 4:1 males to females; Increased risk in siblings or offspring of affected individuals; Recurrence risk is higher for males than females