Ch. 26 - Genomics

who are genetic counselors

people that help individuals understand modes of inheritance and medical consequences of genetic disorders

what is karyotyping

a visual display of someone’s chromosomes

what is amniocentesis

a prenatal test

what occurs in amniocentesis?

a sample of amniotic fluid is collected so fetal cells can be isolated and analyzed

what is the chance of spontaneous abortion in amniocentesis

0\.25 - 0.5%

how does chromosome numbers change

nondisjunction

what is a trisomy

an extra chromosome is carried by an egg or sperm

what is a monosomy

an egg or sperm that lacks a chromosome

what does an extra copy of chromosome 21 account for

down syndrome

extra copies of gart genes = ?

more purines in the body

what are characteristics of down syndrome

short stature, enlarged tongue, distinct palm crease

what can cause chromosomes to break apart

radiation, certain chemicals, and some viruses

what is williams syndrome

a chromosome deletion where chromosome 7 loses an end piece

what are the symptoms of williams syndrome

individuals have a turned up nose and a wide mouth with small chin with poor academic skills but amazing verbal and musical skills

what is cri du chat syndrome

a chromosome deletion where chromosome 5 loses an end piece

what are the symptoms of cri du chat syndrome

small head, mental disabilites, cat-like cry

what is chromosomal duplication

when chromosome segment is repeated in same or nonhomologous chromosome

what can also occur to a duplicated chromosome

it can be in an inverted direction - inversion

what is inversion

segment is turned 180 degrees

what does inversion lead to

altered gene activity in crossing-over

what can inversion result in

duplication and deletion when inverted segments loop in crossing-over

what is chromosomal translocation

the exchange of chromosomal segments between two nonhomologous segments

what is alagille syndrome

translocation between chromosomes 2 and 20

what are family pedigrees

chart of family’s history

what are males indicated on pedigrees

squares

what are females indicated on pedigrees

circles

what does shaded shapes mean in pedigrees

individual is affected by disorder

how can we tell if a pedigree is autosomal recessive?

* most affected children have unaffected parents
* heterozygotes (Aa) have an unaffected phenotype
* two affected parents will always have affected children
* affected individuals with homozygous unaffected mates will have unaffected children
* close relatives who reproduce are more likely to have affected children
* both males and females affected with equal frequency

how can we tell if a pedigree is autosomal dominant

* affected children will usually have an affected parent
* heterozygotes (Aa) are usually affected
* two affected parents can produce an unaffected child
* two unaffected parents will not have affected children
* both males and females affected with same frequency

in pedigrees for x-linked disorders, how can a daughter be affected?

must inherit it from both parents

in pedigrees for x-linked disorders, how can sons be affected?

only inherit it from mother, therefore more males affected than females

in y-linked disorders, how can sons be affected

fathers pass trait to all sons (present in only males)

how can we tell if a x-linked pedigree is recessive

* more males than females affected
* affected son can have parents who have normal phenotype
* for a female to have the characteristic, father must have it and mother must have it or carrier
* the characteristic often skips a generation from the grandfather to the grandson
* if a woman has characteristic, all sons will have it

what are 4 autosomal recessive disorders

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

what is tay-sachs disease

lack of hex A enzyme and symptoms appear in the first year of life

what does tay-sachs disease cause

defective lysosomes (especially in the brain)

what is cystic fibrosis

defect in chloride channel proteins in cells (most common genetic disorder for caucasian males in the us)

what does cystic fibrosis cause

thick, abnormal mucus production in lungs, bronchial tubes, and pancreatic ducts

what is phenylketonuria

lack enzymes for phenylanine (1 of 20 amino acids) metabolism

what does phenylketonuria affect

nervous system development (can be controlled with diet)

what is sickle-cell anemia

irregular red blood cells caused by abnormal hemoglobin

what does sickle-cell anemia cause/do

clog vessels - poor circulation and internal hemorrhaging

heterozygous individuals are normal until?

dehydrated or experience mild oxygen deprivation

what are 2 autosomal dominant disorders

marfan syndrome and huntington disease

what is marfan syndrome

a defect in fibrillin-protein in elastic connective tisuse

what does marfan syndrome

long limbs and fingers, weakened arteries, dislocated lenses in the eyes

what is huntington syndrome

progressive degeneration of brain cells

gene for defective protein called huntington

what does huntington syndrome

too many copies of the amino acid glutamine in the protein causes it to change shape and clump in neurons

encourages other proteins to clump

what is familial hypercholesterolemia

incompletely dominant disorder that affects the number of LDL (low-density lipoproteins)-cholesterol receptors on cells

what does familial hypercholesterolemia lead to

high cholesterol and cardiovascular

what would being homozygous for defective gene mean (familial hypercholesterolemia)

have no LDL-cholesterol receptors and develops cardiovascular disease and die as a child or in teenage years

what would being heterozygous for defective gene mean (familial hypercholesterolemia)

would have half the normal amount of LDL-cholesterol receptors and live longer

what would being homozygous for normal gene mean (familial hypercholesterolemia)

normal number of receptors

what percentage of caucasian males have red-green colourblindness

8%

what is duchene’s muscular dystrophy

x-linked recessive disorder that has the absence of a protein called dystrophin

what does duchene’s muscular dystrophy cause

causes calcium to leak into muscle cells which activates enzymes that break down the cells

what is hemophilia A

a lack of clotting factor VIII

what is hemophilia B

a lack of clotting factor IX

what does hemophilia cause

blood clotting to go slow or not at all - can bleed externally or internally leading to hemorrhaging or death (clotting factors are now available)

how do mutations lead to disorders

caused by a missing enzymes

what does tay-sachs disease test for

quantity of hex A enzyme present in a sample of cells

what can a tay-sachs disease test determine

if individual is homozygous normal, a carrier, or has Tay-sachs

what is the PKU test

test done on newborns to determine the presence of phenyalanine

what are 3 ways to test DNA for genetic disorders

genetic markers, dna probes, dna chip

how do we test DNA with genetic markers

in genetic markers, restriction enzymes cleave DNA

what disorder does genetic markers test for

huntington disease

how do we test DNA with dna probes

a DNA probe (single stranded piece of DNA) binds to complementary DNA

in genetic testing, what do dna probes typically have

mutation of interest

how do we test DNA with dna chip

tagging person’s DNA with fluorescent dye and convrted to single stranded DNA before being applied to the chip

what occurs on the dna chip during testing

mutated genes bind if present and are detected by laser scanner

how do we test a fetus

ultrasound

what is an ultrasound

high frequency sound waves used to produce an image

when are fetal cells tested for in amniocentesis

15 weeks of gestation (process or period of development inside womb between contraception and birth)

what can amniocentesis also test for

alpha fetoprotein which can indicate neural tube defects

when can fetal cells be tested during chorionic villi sampling

earlier than amniocentesis (no amniotic fluid taken so cannot test for afp

how can fetal cells in mothers blood be tested

when a small number of fetal cells enters the mother’s blood

how can an embryo be tested

at the 8-cell stage following in vitro fertilization

* only “normal” embryos are tested

how are eggs tested

by testing the polar bodies of women who are heterozygous prior to in vitro fertilization

if a polar body is defected, what occurs to the ovum

ovum is normal

what is genomics

study of genomes

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what is a genome

complete set of DNA in an organism

how many genomes do humans have

20,000 - 25,000

what is the human genome project

a project that wanted to sequence all of the base pairs in all of the DNA of human chromosomes

* also revealed that humans probably have 20,000 - 25,000 genomes

what was the objective of the hapmap project

to catalog common sequence differences that occur in humans so scientists can link haplotypes to the risk of specific illnesses

what are haplotypes

patterns of sequence differences

what are proteomics

study of structure, function, and interaction of cellular proteins

what is a proteome

translation of all human genes resulting in a collection of proteins

how does the info computer modeling provide about the shape of proteins help

allows for greater understanding of how they work and increased efficiency of drugs

what is bioinformatics

application of computer technologies to the study of genome

what occurs in bioinformatics

an analysis of data produced by genomics and proteomics

what is the human genome described as

three-dimensional

what is the first dimension of the human genome

the sections of DNA that codes for proteins (accounts for less than 2% of DNA)

what is the second dimension of the human genome

“junk DNA” that may code for RNA

what is the third dimension of the human genome

outside layer that surrounds DNA and consists of proteins and other chemicals

what is gene therapy

insertion of genetic material into human cells for treatment of a disorder

what is vivo gene therapy

when cells are removed from the patient and those cells are treated outside the body then returned back

what is an example of vivo gene therapy

SCID (severe combined immunodeficiency) and cystic fibrosis

what occurs in vivo gene therapy

patient is given a foreign gene directly through viruses or lipoprotein vesicles

where is the foreign gene of vivo gene therapy incorporated within

the genome within the body