Patho: Genes and Genetic Disorders

Genetic information is stored in ...?

chromosomes

How many pairs of chromosomes are there?

23 pairs/ 46 individual chromosomes

How many autosomes do we have?

22 autosomes

How many sex chromosomes do we have?

2/ 1 pair (XX, XY)

Chromatin

Strand of nucleosomes

Chromosomes

2 pairs of chromatid

Gene

a unit of heredity

Locus

fixed position of a gene

Alleles

Variation of a gene

Genotype

genetic code

Phenotype

expression of gene

Homozygous genes

HH, hh

Heterozygous genes

Hh

Examples of autosomal dominant disorders

Huntington's and Marfans

Example of autosomal recessive disorders

cystic fibrosis, sickle cell, phenylketonuria, tay- sachs disease

Examples of X- linked dominant disorders

fragile x syndrome

Examples of X - linked recessive disorders

color blindness, Dutchman's muscular dystrophy, hemophilia A, Alport's syndrome

Examples of chromosomal disorders

down syndrome (trisomy 21), turners syndrome (monosomy X), edwards syndrome (trisomy 18)

Genetic disorders are often inherited due to...?

chromosomal defects, single gene disorders, polygenic (multifactorial)

Chromosomal aberration

Entire chromosome is abnormal

Euploid

Normal number and pairs of chromosomes (23 pairs, 46 chromosomes)

Aneuploidy

the presence or absence of one or more chromosomes

Types of aneuploidy

Monosomy: 1 copy of chromosome (lethal)

Trisomy: 3 copies of chromosome (can survive)

*better to have extra than less

What causes aneuploidy?

Non-disjunction

Non-disjunction

Failure of chromosomes to separate during cell division

Examples of autosomal aneuploidy

down syndrome

Example of sex chromosome aneuploidy

turner syndrome

Down syndrome is the best example of...?

Non-disjunction

Risk for down syndrome

maternal age over 35

Characteristics of down syndrome

epicanthal fold

malformed ears

congenital heart disease

leukemia

wide gaps in toes

short hands

intestinal malformation

big protruding tongue

mental retardation (spectrum)

Turner syndrome

Female who only has one X chromosomes, X chromosome is inherited from mom

Characteristics of turner syndrome

underdeveloped ovaries

short stature

webbing of neck

edema

underdeveloped breast

wide nipples

high number of aborted fetus

normal neurological function

Single gene disease: Mode of transmission

Autosomal dominant: 1 defective gene

Autosomal recessive: 2 defective genes

X-linked dominant and recessive

Recurrence risk

Probability an individual will develop a genetic disease, each child has a 50% chance of getting the disease

Recurrence risk example

Hh + hh= Hh (50% affcted) , hh (50% carriers)

Penetrance

probability of gene or trait being expressed

Example of penetrance

Retinoblastomas

Only some children having blue eyes instead of all

Incomplete penetrance

has gene but does not express the disease

Expressivity

variation in phenotype expression

Example of expressivity

Hemophilia (mild or severe)

Children having different color eyes instead of all blue

Autosomal dominant inheritance

Inheritance of one defective allele cause disorder, only one parent has to carry the defective gene

Autosomal dominant inheritance characteristics

no carriers, doesn't skip generations, conditions can become evident later in life

Autosomal dominant inheritance examples

huntingtins, marfans, von reckling ,von willebrands

Hh + hh= Hh( 50% affected), hh(50% normal)

Autosomal recessive inheritance

both parents pass on defective alleles

Hh= Carrier, hh= affected

What is the recurrence risk for autosomal recessive inheritance?

25%, male and females are affected equally

Autosomal recessive disorder examples

Cystic fibrosis

sickle cell anemia

tay sachs

Consanguity

mating between relatives

Sex linked inheritance (X- linked)

Genetic conditions caused by mutations on sex chromosomes, usually the X chromosome, recessive disorders being the most common

Who is affected in X-linked disorders

Males, they can affect their son but can pass it to their daughters (carriers)

Females and X-linked disorders

Are either carriers or normal, sons of females have a 50% chance of getting the disease

Multifactorial inheritance

Genetic influences combined with environmental factors

Examples of multifactorial disorders

Anencephaly ,Cleft lip and palate, Clubfoot, Congenital heart disease, Myelomeningocele, Schizophrenia