Genetics Lecture 1: Human Mendelian Genetics

Front 1

Types of single gene (mendelian)

Back 1

Autosomal dominant
Autosomal recessive
X-Linked dominant
X-link recessive

Front 2

Locus

Back 2

Specific location of a gene on a chromosome. (ex. 15q21.1) P = petite side, Q = larger side.

Front 3

Alleles

Back 3

Alternative forms of a gene at a given locus.

Front 4

Compound Heterozygous

Back 4

2 different abnormal alleles at one locus in one individual.

Front 5

Geneotype and phenotype

Back 5

Genotype = genetic makeup
Phenotype = observed characteristics

Front 6

Characteristics of autosomal dominant inheritance

Back 6

1) Only one copy of mutant allele is necessary for expression of trait.
2) Heterozygote has a 50% chance to pass on mutant allele.
3) Homozygous offspring are at no risk

Front 7

Characteristics of autosomal dominant pedigree

Back 7

1) Transmission is from generation to generation.
2) boys and girls equally affected
3) Male to male transmission is possible
4) Unaffected individuals (usually) have unaffected children

Front 8

Penetrance

Back 8

% of individuals with the mutation who have signs of the disease. Can be complete of incomplete

Front 9

Obligate Heterozygote

Back 9

Someone who has affected mother and children but no symptoms himself. Probably because of incomplete penetrance.

Front 10

Pleiotropy

Back 10

Multiple phenotypic effects in different tissues an organs from a single gene mutation

Front 11

De novo mutation

Back 11

Unaffected parents have a child with a dominant disorder.

Front 12

What causes an increase in risk of autosomal dominant de novo mutations?

Back 12

Age of father because sperm stem cells replicating throughout life, have increase chance for a mutation.

Front 13

Germline mosaicism

Back 13

When a mutation occurs in some of the gonadal tissue but not the somatic tissue. Causes unaffected parents to have affected child. If present, phenotypically normal parents have higher chance of having multiple affected children.

Front 14

Causes for variable expression

Back 14

1) Enviromental factors
2) Modifying background genes
3) Genetic Heterogeneity (allelic or locus)

Front 15

Allelic heterogeneity

Back 15

Different types of mutations at the same locus can result in variable expression of the genes.

Front 16

Locus Heterogeneity

Back 16

When a disease phenotype is caused by a mutation of genes in different loci.

Front 17

Anticipation

Back 17

Tendency for a certain disease to show progressivly earlier onset and increasing severity in successive generations. Caused by increase in trineucleotide repeats.

Front 18

Characteristics of autosomal recessive inheritance

Back 18

1) Two copies of mutant allele are necessary
2) Heterozygotes are completely normal.
3) 2 carrier parents have a 25% chance of having affected child regardless of gender.
4) Unaffected offspring have 67% chance of being carriers.
5) All offspring of affected individual will be carriers.

Front 19

Characteristics of autosomal recessive pedigree

Back 19

1) Disorders rarely present in parents but may be in siblings
2) Number of affected males and females equal
3) Consanguinity is more likely to be present.

Front 20

Consanguinity

Back 20

Relationship with relative. More common in people who have rare autosomal recessive disorders.

Front 21

Clinical characteristics of autosomal recessive disorders

Back 21

1) Cluster in ethnic groups with geographic or religious isolation.
2) Penetrance is usually complete and there is less phenotypic variability than dominant.
3) Most AR are enzyme abnormalities.
4) Can have genetic heterogeneity

Front 22

Why are there rarely individuals with 2 dominant mutant alleles?

Back 22

Usually it is not compatible with life.