BLD 204: Genetic Disorders

congenital

congenital: being born with a disorder but not necessarily inherited (meaning the mutation was NOT in the egg or sperm's DNA at conception).

ex: Fetal alcohol syndrome-->the baby's DNA is messed up because mom drank alcohol while being pregnant. The DNA at conception was completely normal and the baby would have been normal if mom didn't drink.

hereditary

Passing of traits from parents to offspring

Genotype

An organism's genetic makeup, or allele combinations.

Phenotype

An organism's physical appearance, or visible traits.

types of genetic abnormalities

cytogenetic (chromosomes) and single gene defects

also to mention: epigenetic changes, multi-factor disorders, and alterations in non-coding RNA

cytogenetic

chromosomal genetic disorders analyzed through karyotyping

Karotyping

Test used to determine if the chromosomes are normal in structure & number

karyotype analysis

source of chromosomes: lymphocytes, amniotic fluid, bone marrow
- cells are encouraged to enter mitosis, chromosomes are separated from cells
suspension is put on slides to stain bands on regions of chromosomes

- naming (1)chromosome number (2) short or long arm: P or q (3) group that band is in (4) number of band in group
5q34

Cytogenetic abnormality

1 in 200 newborns, higher in pregnancies that don't make it to full term (think of miscarriage, aka non- survivable genetic mutations).

prenatal screening vs prenatal diagnostic testing

screening: blood tests looking at fetal DNA, and ultrasound
- don't give enough information for diagnosis, need a diagnostic test

diagnostic:
-chronic villus sampling: material from the placenta
- amniocentesis: amonotic fluid
- Percutaneous umbilical blood sampling: umbilical cord blood

genetic factors that contribute to cytogenetic disorders recognizable on karyotype exam

- translocation- chromosomes swap parts

- isochromosomes- chromosomes come apart at centromere so tops become new chromosomes and bottoms come together to make new chromosome

- big deletions: self-explanatory

- ring chromosome- a bunch of DNA is cut out and rest sticks together to make ring

polyploidy

additional whole haploid set, 69 instead of 46

aneuploidy mutation

not a multiple of 23
- Trisomy: extra chromosome
- Monosomy: loss of one from a pair

autosomal vs sex linked disorders (chromosomes involved)

autosomal- other 22 pairs
sex-linked- on X chromosome, not usually on the 7

autosomal dominant

only one gene needed to express

the parent is affected or heterozygous (unless de novo)
phenotype expressed at same rate in males and females
showing up in every generation almost
regulatory proteins and structural proteins affected

autosomal recessive

two copies of an abnormal gene must be present in order for the disease or trait to develop

-parents are alteast heterzogous
-parents may not have mutations but siblings may
-penetrance is usually complete
-frequency of mutant phenotype for males and females

sex-linked recessive

genetic conditions associated with mutations in genes on the X chromosome.
A male carrying such a mutation will be affected, because he carries only one X chromosome.
A female carrying a mutation in one gene, with a normal gene on the other X chromosome, is generally unaffected.

Common types of single gene mutaitons

deletions, duplications, insertions, fusions, point mutations

Gene Deletions- A-Thalassemia

Disease of red blood cells. Number of deletions relate to severity of disease

normal: Hgb requires two pairs of a globin genes
loss of one copy: a-thalassemia trait
two copies lost: HbH disease
loss of all copies: hydrops fetalis

Partial Gene Deletions

part of code is deleted, but some protein may be translated

ex. Duchenne's muscular dystrophy- dystrophin gene partial deletion, but it's a huge gene. causes frameshift mutation making part of it inactive

Whole Codon Deletions

Loss of amino acid, NOT alteration of reading frame. results in improper folding and affect function

ex. Cystic fibrosis, common mutation deletion in one codon for phenylalanine for chloride transporter

Nondisjunction deletion

pairs of homologous chromosomes or sister chromatids fail to separate during meiosis

Duplicaitons

stutter of polymerase during replication

result is dependent on what gene it changes

Insertions

Usually the result of unequal crossover of translocation, can shift reading frame

Fusions

unequal crossing-over between non-homologous chromosomes results in two genes fusing

ex. Red/Green color blindness, results from the fusion of red and green pigment detecting genes when unequal crossing over occurs during meiosis

incomplete penetrance

individual with dominant mutant genotype presents a normal phenotype
#experssing/#possesing does not = 1

point mutaitons

you know this from your last microbio exam bitcchhhhh

inversion

when a chromosome breaks in two places; the resulting piece of DNA is reversed and re-inserted into the chromosome

translocation

when a piece of one chromosome breaks off and attaches to another chromosome

modes of inheritance of familial hypercholesterolemia (autosomal dominant)

LDL receptor defect, LDL cannot remove LDL, premature atherosclerosis

mode of inheritance for phenylketonuria (autosomal recessive)

Defect in enzyme that breaks down phenylalanine
builds up causes brain damage
newborn screening prevents problem

hemophilia A- x linked

Factor VIII (this is factor 8 lol) deficiency in Coagulation pathway, causes bleeding problems
on X chromosome

Autosomal recessive- a1-antitrypsin

lots of elastase produced from neutrophils to remove inflammation, a1-trypsin gets rid of elastase

w/o removal can cause emphysema
allele: M S Z

autosomal recessive- tay-sachs

accumulation of gangliosides due to lack of lysozyme causing brain damage

unfolded protein response- results in apoptosis

Galactosemia

Galactosemia is a rare, hereditary disorder of carbohydrate metabolism that affects the body's ability to convert galactose to glucose

Fragile X (triplet repeat mutations)

Mutation: CGG triplet relates in FMR1

Triplet repeat mutations

amplification of a specific set of three nucleotides within the gene disrupts its function (fragile X syndrome)