Genetics Mendel

Genetics

study of genes and how they are inherited

determined by parents

Genes

como in alleles

encode phenotypes

located in chromosomes

Locus

specific physical location of a gene

Loci

plural of locus

Homozygote

tow same alleles

Heterozygote

two different alleles for same gene

Genotype

individual’s complete set of genes they have inherited from parents

Phenotype

physically observable

Missense mutation

encodes for different aminoacidq

Nonsense mutation

Encodes for stop codon

Frameshift mutation

changes some codons

Mutations

result in gain or loss of function

Gain of function

seen in dominant diseases

Loss of function

seen in recessive diseases

Monogenic diseases

produced by mutations in a single gene

Multifactorial diseases

produced by interaction between group of genes and environmental factors

ie Diabetes II

Chromosomal rearrangements

produced by alteration in number of chromosomes or by their structure

Segregation law

Every individual organism contains 2 alleles for each trait such as when they separate each gamete contains one of them

Mendel’s first law

Two members of a gene pair segregate from each other into the gametes

Mendel’s second law

different gene pairs assort independently in gamete formation

Independent assortment

genes at different loci are transmitted independently

Pedigree structure

No color

3 generations at least

Name age dob

Diseases

Male, Female, Unspecified

Proband (consultand)

Deceased

Affected with trait

Carrier (autosomal or x-linked recessive)

Asymptomatic (autosomal dominant)

Adopted

Consanguinity

Dizygotic twins

Monozygotic twins

First degree relatives

Second degree relatives

Third degree relatives

Autosomal Dominant Inheritance

Unaffected parent + Affected Heterozygote parent

No skip generations

If neither parent has the trait, none of the children will have it

50/50

Recurrence risk for

Affected heterozygote and unnafected

50% will be affected

Recurrence risk for

Affected heterozygote + affected heterozygote

75% affected

Recurrence risk for

Affected homozygote+ unnaffected

100% affected

Recurrence risk for

Affected homozygote + affected homozygote

100% 50 het 50 homo

Familial hypercholesterolemia

LDLR gene

19p13.1

APOB and PCSK9 genes

High cholesterol

Artherosclerosis

Xanthomas

Achondroplasia

Dwarfism

Autosomal dominant

Mutation in FGFR3 gene (4)

Gain of function for the protein

Homozygous is usually lethal

Hereditary Multiple Exostoses (M. Osteochondromas)

Multiple benign cartilage-capped bone tumors

Autosomal dominant

EXT1 or EXT2

Risk of chondrosarcoma

Marfan Syndrome

Connective tissue disorder

Autosomal dominant

FBN1 gene (fibrillin-1)

Tall stature/extremities

Aortic root dilation

Beta blockers reduce risk of aorta complication

Neurofibromatosis Type 1 (NF1, von Reckling)

Neurocutaneous

Autosomal dominant

NF1 gene (neurofibromin)

Freckling

Optic gilomas

Malignant tumors

Variable expressivity

Tuberous Sclerosis Complex

Hamartomas

Autosomal dominant

TSC1 (hamartin)

TSC2 (tuberin)

mTOR pathway dysregulation

Ash leaf spots

Subependymal giant cell astrocytoma (SEPA)

Everolimus (mTOR inhibitor)

Autosomal recessive inheritance

We must have carriers to present disease

Horizontal transmission

Consanguinity is present

Cystic Fibrosis

CFTR gene

7q31.2

Chloride ion transport defect

Phenylketonuria (PKU)

Inborn error of amino acid metabolism

Autosomal recessive

Mutation in phenylalanine hydroxylase

Accumulation of phenylalanine

Low phenylalanine diet, avoid aspartame

Tay Sachs

Lysosomal storage disorder

Autosomal recessive

Deficiency of hexosaminidase A

GM2 ganglioside accumulation

Cherry red spot macula

NO hepatosplenomegaly

Early death

Wilson disease

Copper metabolism

Autosomal recessive

ATP7B

Copper accumulation

Kayser-Fleischer rings

Chelation and Zinc

Xeroderma pigmentosum

DNA repair disorder

Autosomal recessive

Nucleotide excision repair

UV induced damage

Incomplete penetrance

person who has a disease-causing genotype might not exhibit the disease phenotype at all

Variable expression

degree of severity of disease phenotype

Allelic heterogeneity

different types of mutations at the same disease locus

Locus heterogeneity

mutations at different loci in different families

Pleiotropy

genes that have more than one discernible effect on body