Ch 5: Genetics Flashcards
what is mitosis
splitting of a diploid parent cell
DNA replicates to form two identicle, dipoid daughter cells
makes somatic (body cells)
does not make gametes
what is meiosis
diploid parent cell copies itself then goes through two rounds to eventually split into 4, unidenticle daughter haploid cells
makes sex cells and no other type of cells
what are the products of mitosis
2 identicle diploid daughter cells
what are the products of meiosis
4 unidenticle haploid daughter cells (gametes)
what are somatic cells for
tissue growth and rapir
what is a diploid (2n) cell
somatic body cell with a nucleus that has 46 chromosomes (2 sets of 23 - one from each parent)
which chromosomes are autosomal
all those not including the sex cells (1-22)
what is a karyotype
map that shows and sorts the 23 pairs of chromosomes
what is chromatin
DNA that is not dividing
what is the overall shape of a chromsome
made of tightly packed DNA helices woven around histones
two sister chromosomes combine in the middle at the centromere
what does it mean when the sister chromatids are not connected at the centromere
they have not yet gone through replication
each chromosome in a homologous pair has what
the same genes
what is a gene
linear segments of nucleotide bases that code for specific proteins ex. CFTR protein
what is an allele
specific regions on a chromosome that can code for different things such as hair color
these can differ between each chromosome in a homologous pair
what are the two types of arms on a chromosome
p arm (shorter)
q arm (longer)
what is euploid
cells with a multiple of the normal number of chromosomes
ex. haploid, diploid, and polypoidy
what is haploid
a cell with only one set (23) of chromosomes
what is triploidy
when you have 3 multiples of the normal number of chromosomes
ex. 69 chromosomes (23 (normal) X 3 = 69)
what is tetraploidy
when you have 4 multiples of the normal number of chromosomes
ex. 92 chromosomes (23 (normal) X 4 = 96)
how many homologous pairs of chromosomes do males have
22 because their sex chromosomes (XY) are not homologous
what is aneuploid
condition of having an abnormal number of chromosomes in a haploid (23) set
usually caused by a non-disjunction during meiosis
ex. trisomy and monosomy
what is trisomy
when an individual has an extra chromosome in a set of 23
ex. down syndrome sufferers have an extra copy of the 21st chromosome
what is monosomy
when an invidvidual is missing a chromosome in a set of 23
ex. turner’s syndrome sufferers are females missing the X sex chromosome
what is a non-disjunction mutation
sister chromatids fail to separate properly
mitosis: chromosome splits but both stay in one cell
meiosis: chromosomes don’t split during meiosis 1
explain the very basics of transcription
in the nucleus, introns from a mRNA strand are removed and a cap and tail are added
mature mRNA strand can now leave the nucleus to help read codons during translation
what is a codon
group of 3 nucleotides from a DNA and RNA strand that determine which type of amino acid (protein) will be made
how many amino acids are there and why do they lead to so many different proteins
20
can make so many different proteins because different combinations of them will lead to different products
what is the start codon
AUG (methionine)
what are the three stop codons
UAA, UAG, and UGA
what causes folding in amino acids
interactions with their unique biochemistries
what percentage of spontaneous abortions in early months of gestation are due to chromosomal abnormality
50%
what are mendelian disorders
disorders caused by a mutation in a single gene that has very large effects
generally rare but very informative about physiological mechanisms
what are chromosomal disorders
disorders that arise from structural or numerical alteration in the chromosomes
what are complex multigenic disorders
most common type of human genetic disorders
caused by interactions between multiple
alleles and the environment
ex. atherosclerosis, autoimmune disorders, and diabetes
what is a mutation
a permanent change in the DNA
what happens when there is a mutation in germ cells
it can be passed to offspring
what happens when there is a mutation somatic cells
mutation does not cause hereditary diseases but can give rise to cancer and some congenital malformations
what is a point mutation
when one nucleotide of a codon is replaced for another
ex. silent, nonsense, and missense
what is a silent point mutation
a type of point mutation where a single nucleotide is replaced with another
does not change amino acid
what is a nonsense mutation
a type of point mutation where a single nucleotide is changed, making it a stop codon
ex. beta 0-thalassemia
what is a missense mutation
a type of point mutation where a nucleotide is replaced with another and it changes the amino acid
can either be conservative or nonconservative
what is a conservative missense mutation
when the changed single nucleotide changes the amino acid to another similar one
ex. one polar amino acid changes to another polar amino acid
what is a nonconservative missense
when the changed single nucleotide changes the amino acid to a different amino acid
ex. one polar amino acid changes to a nonpolar one
ex. sickle cell anemia
what happens when multiples of three bases are added to or deleted from a reading frame
it remains intact
an amino acid is either gained or lost
what is a frameshift mutation
when there is an addition or deletion of a number of bases that is not a multiple of 3
causes a new read out that has shifted
can lead to a premature stop
what happens when there are mutations in regulatory elements such as enhancers and promoters
transcription is altered
ex. thalassemia
what happens when there are mutations in introns
leads to defective splicing which means mature mRNA cannot be produced
leads to no protein being produced
what happens when there is an amplification of repetitive sequences
prevents normal gene expression
usually G or C nucleotides
ex. CGG repeating in familial mental retardation 1 (FMR1)
what is fragile X syndrome (FXS)
individuals with 250-4000 sequence repeats on the X chromosome
causes intellectual disability
what happens when the number of chromosome copies changes
more copies - amplification
less copies - deletion
both can cause gain or loss of protein function
what happens when there is a translocation of a chromosome
regions of two chromosomes are switched
can be balanced/unblanced or Robertsonian
ex. Philadelphia chromosome t(9;22)
what is Philadelphia Chromosome
a translocation where the abl gene inserts and fuses into the bcr gene
fused genes now function improperly leading to chronic myelogenous leukemia (CML)
what are four other types of diseases (besides philadelphia chromosome) than can arrise from translocation
diffuse large B-cell lymphoma
burkitt lymphoma
mantle cell lymphoma
follicular lymphoma
what happens when there are alterations in noncoding RNA transcripts (ncRNA)
alterations affect their ability to produce transcripts and serve as important protein regulators
ex. micro RNA (miRNA) and long noncoding RNA (lncRNA)
which man is known for his work analyzing patterns of inheritance
Gregor Mendel
define heredity
transmission of traits from one generation to the next
define genetics
the study of heredity
what is a character
inheritable feature that varies among individuals
ex. flower color and seed shape
what is a trait
a variant of a character
ex. purple or white flowers, round or wrinkled seeds
what is phenotype
observable characteristic
ex. height and eye color
what is genotype
genes that are inherited
what was the first hypothesis regarding monohybrid crosses
there are different types of genes (alleles) for a specific inherited character
ex. flower color gene either comes in purple or white
what was the second hypothesis regarding monohybrid crosses
law of segregation
gametes carry one allele for each inherited character
they get one from mom and one from dad
what was the third hypothesis regarding monohybrid crosses
organism inherits two alleles, one from each parent
alleles could be identical or different
define homozygous
two identical alleles
define heterozygous
two different alleles
what was the fourth hypothesis regarding monohybrid crosses
if the two inherited alleles are different, one will determine the organism’s appearence
what is galactosemia
recessive disorder where the body cannot convert galactose to glucose so there is a buildup
what is a pedigree
genetic representation of a family tree that diagrams the inheritance of human traits or disease through several generations
what does congenital mean
something you are born with
define de novo
disorder that starts after gamete is formed (not inherited)
define pleiotropy
a single mutant gene leads to many phenotypic effects
ex. Marfan’s syndrome affects eyes, skeleton, heart, etc.
define genetic heterogeneity
mutations at several genetic loci produce the same trait
ex. different mutations can lead to retinitis pigmentosa
what is retinitis pigmentosa
eye disease that leads to vision loss
example of genetic heterogeneity
what do Y-linked disorders lead to
infertility - they cannot be passed down
what is vitamin D resistant rickets
X-linked dominant disorder that leads to painful and soft bones due to low levels of vitamin D
what is Alport Syndrome
X-linked disorder that affects kidneys, ears, and eye
which percentage of offspring will have a chance of inheriting a disease if they have one affected parent and one carrier parent
50%
Aa crossed with aa
is age of onset delayed in dominant or recessive diseases
dominant
what is reduced (incomplete) penetrance
a proportion of individuals who carry mutant gene are phenotypically normal
ex. 15% of those with BRCA1 gene do not get cancer
what is variable expression
when individuals with the same mutant gene express different phenotypic traits
ex. neurofibromatosis type 1 (von Recklinghausen disease)
what is Neurofibromatosis (von Recklinghausen disease)
dominant
type 1: NF1 gene is affected which leads to an abnormal tumor supressor neurofibromin protein; leads to cutaneous benign neurogenic tumors
type 2: NF2 gene is affected which leads to an abnormal merlin protein; leads to benign acoustic neurogenic tumors
what is Huntington Disease
dominant
40+ CAG repeats affect the HTT gene which leads to an excessive amount of huntingtin protein
build up of huntingtin protein is toxic to neurons and causes progressive neurodegenerative disorders
what is the most common class (dominant or recessive) of mendelian disorders
recessive
what is the % of offspring being affected by a recessive disorder when both parents are carriers
25%
Aa and Aa
what is a consanguineous marriage
marriage between two blood relatives
leads to more recessive disorders
what is Cystic Fibrosis
recessive
CFTR gene is affected which leads to abnormal CFTR proteins
abnormal CFTR proteins leads to impaired anion transport which causes injury to lungs and pancreas
what is Sickle Cell Anemia
recessive
point mutation in the HBB gene which leads to an abnormal beta-globin protein
abnormal beta-globin leads to sickling of blood cells and eventually splenomegaly
what is Tay-Sachs
recessive
mutation in the HEXA gene which leads to deficiency of beta-hexosaminidase enzyme
GM2 ganglioslides now build up in many different tissues
presents with: cherry red spot on retina, muscle issues, and dementia
death between 2-3 years of age
what is the % of offspring that will have an X-linked disorder if they have a carrier mother and non-affected father
50%
XHXh and XHY
X-lniked disorders are usually recessive
what is Duchenne Muscular Dystrophy
X-linked disorder
mutation in the dystrophin gene of the X chromosome
mutation in this important structural protein in striated skeletal muscle leads to structural deformities and membrane rupture
what is Red-Green Color Blindness
X-linked recessive
malfunction of light-sensitive cells in the eyes
more frequent in males
what is Hemophilia
X-linked recessive
blood clotting disorder
A: mutation leads to reduced production of clotting factor 8
B: lack of clotting factor 9
what is Marfan Syndrome
dominant
defect in fibrillin-1 due to a mutation in FBN1 gene
leads to either loss of structural support or excessive activation of TGF-beta signaling
affects microfibrils in aorta, ligaments, and ciliary zonules
presents with: long extremities, hyperextensible joints, spinal deformities, ectopia lentis, valve issues, and pectus excavatum
what is extopia lentis
bilarteral dislocation of the lens
what is the importance of fibrillin-1
it is a major component of microfibrils found in extracellular matrix
makes scaffolding for deposition of elastic fibers
what is Ehlers-Danlos Synrome
disorders resulting in genes that encode collagen, enzymes that modify collagen, or other proteins in the extracellular matrix
presents with: hyperextensible skin, hypermobile joints, and internal complications of the colon, cornea, and large arteries
what do lysosomes do
function as intracellular digestive system
autophagy, immunity, and membrane repair
contain acid hydrolases
what are acid hydrolases
specialized enzymes that function in acidic fluid within lysosomes
targeted to lysosomes by mannose-6-phosphate tag attached in Golgi
what type of mutation are most lysosomal storage diseases
mutation in a single enzyme
usually autosomal recessive
what is primary accumulation in lysosomal disorders
mutation in a lysosomal enzyme causes undigested macromolecules to build up inside of lysosomes
this accumulation interferes with normal cell function
ex. Gaucher disease
what is secondary accumulation of lysosomal disorders
primary defect outside of lysosome causes substances that are normally degraded by autophagy to build up in the cytoplasm
ex. Nieman-Pick type C
what is Gaucher Disease
most common lysosomal storage disease
mutation in glucocerebrosidase leads to an accumulation of glucocerebrosides in the phagocytes and nervous system
cytokines are secreted by macrophages in response to accumulation
what is Guacher Disease Type 1
most common type of Guacher disease
chronic non-neuropathic form
reduced levels of enzymatic (glucocerebridase) activity leads to spleen and skeletal involvement but normal life expectancy
what is Gaucher Disease Type 2
infantile acute cerebral pattern
no enzymatic activity
causes hepatoplenomegaly and progressive CNS involvement
leads to death at an early age
what is Gaucher Disease Type 3
intermediate form
progressive nervous disease with systemtic involvement
starts in childhood
what is Niemann-Pick Disease Type A
deficiency in sphingomyelinase which leads to an accumulation of sphingomyelin in lysosomes
severe infantile form that causes extensive neurological invovlement and death by 3 years
what is Niemann-Pick Disease Type B
deficiency in sphingomyelinase which leads to an accumulation of sphingomyelin in lysosomes
enlarged organs with no CNS involvement
survive into adulthood
what is Niemann-Pick Disease Type C
defect in cholesterol transport which leads to accumulation of cholesterol and gangliosides in nervous system
presents with ataxia (no coordination), dysarthria (motor speech disorder) and psychomotor regression
what are the three ways to treat lysosomal disorders
enzyme replacement therapy
substrate reduction therapy
molecular chaperone
what is enzyme replacement therapy
used to treat lysosomal disorders
most widely used
what is substrate reduction therapy
used to treat lysosomal disorders
substrate that’s accumulated is reduced to hopefully allow the residual enzyme to perform better
what is molecular chaperone
used to treat lysosomal disorders
competitive inhibitor that binds to an enzyme to help it fold properly
used in Guacher disease
what is mosaicism
mitotic erros give rise to two or more populations of cells with different numbers of chromosomes
occurs during cleavage or in somatic cell
mostly affect sex cells
what is a terminal deletion
a deletion in the terminal end of a chromosome
what is an interstitial deletion
deletion in the middle of a chromosome
what is a balanced reciprocal translocation
swapping of a portion of a chromsome
chromosomes still end up being the same length as they were before
what is a robertsonian translocation
two chromosomes are stitched together and the short P arms are lost
what is a ring chromosome structural abnormality
chromosome bends into a ring shape and some of it is lost
what are isochromosome abnormalities
P and Q arms of chromosomes break off to become their own chromosome
what is trisomy
an extra chromosome that causes most patients to not survive to full term
what is trisomy 13
Patau syndrome
presents with: extra fingers, cleft palatte, and rockerbottom feet
what is trisomy 18
Edwards syndrome
presents with: horseshoe kidney and rockerbottom feet
what is the average incidence of down syndrome
1 in 700 births
how does age affect the likelihood of having a Down Syndrome baby
as you get older, the chance goes up
how many Down Syndrome babies are spontaneously aborted or stillborn
2/3rds
what is the cause of 95% of those with Down Syndrome
extra chromosome from the mother
what are some clinical features of Down Syndrome
heart defects - usually spetal
increased risk for Hirschsprung’s and Alzheimer’s disease
increased risk for respiratory infections
increased risk for thyroid autoimmune disorders
increased risk for acute leukemia’s
IQ between 25-70 (mental retardation)
what is Hirschsprung’s disease (generally)
poor development of enteric nervous system which affects the ability of the intestines to contract
can be seen in Down Syndrome sufferers
what is Klinefelter’s Syndrome
male develops extra X chromosome (XXY)
presents with: long legs, small testis (hypogonadism), reduced male secondary sexual characteristics, increased estrogen levels, and infertility
what is Turner’s Syndrome
most common cause: female is missing one X chromosome or it’s very deformed (isochromosome)
presents with: underdeveloped ovaries, lack of breasts, peripheral lymphedema, webbing of neck, widely spaced nipples, and coartation (narrowing) of aorta
what do patients with XXX or XXXX present with
no physical abnormalities
sterility or mental retardation
what do patients with XYY present with
taller
slight reduction in IQ
behavioral abnormalities
what is Cri Du Chat Syndrome
most commonly caused by deletion of short arm of chromosome 5
presents with: abnormal vocal cord structure, low birth weight, heart defects, facial abnormalities, and severe mental retardation
what is genetic sex
determined by present or absence of Y chromosome
ex. male or female
what is gonadal sex
histological presence of gonads
what is ductal sex
presence of derivates of mullerian or wolffian ducts
what is phenotypic sex
appearance of external genitalia
what is a true hermaphrodite
someone who has both testicular and ovarian tissue
what is a pseudohermaphrodite
disagreement between phenotypic and gonadal sex
ex. someone having testicular tissue but female genitalia
what is a female pseudohermaphrodite
someone with ovaries and male external genitalia
46, XX
caused by overexpression to androgens during early gestation
what is a male pseudohermaphrodite
someone with testicular tissue but female external genitalia
46, XY
caused by lack of androgen exposure
define genetic imprinting
epigenetic process where there is selective inactivation (silencing) of either the maternal or paternal allele during gametogenesis
what is the mechanism of genomic imprinting
gene expression supression by preventing transcription
methylation at CG nucleotides or DNA is not unwound from histones
both prevent transcription
imprintations passed down to all somatic cells from the zygote
if it causes a loss of function, we get disease
what is Prader-Willi Syndrome
disease caused by loss of active genes (imprinting) on the paternal chromosome
SNORP genes are affected
presents with: intellectual disability, short stature, hypotonia (decreased muscle tone), profound hyperphagia (extreme continuous hunger), hypogonadism (little sex hormone production), obesity, and small hands and feet
what is Angelman Syndrome
UBE3A gene on maternal chromosome is silenced
presents with: intellectual disability, microcephaly (small head), seizures, ataxic gait (can’t walk straight), and innappropriate laughter
“happy puppets”
what are the three prenatal methods to perform genetic testing
amniocentesis, chorionic villus biopsy, and cell free DNA
what is an amniocentesis
needle put into stomach into the amnion to draw fluid for prenatal genetic testing
what is chorion villus sampling
probe put into the vagina to take a sample of the chorion for prenatal genetic testing
what is cell free DNA
taking a maternal blood sample to perform prenatal genetic testing
how is genetic testing done postnatal
a blood sample is taken from both child and parent to test for peripheral blood lymphocytes
what are the three tests that detect structural abnormalities of chromosomes
karyotyping
flourescence in situ hybridization (FISH)
cell free DNA (liquid biopsy)
what does FISH test for
gain, losses, or translocations within chromosomes
what does a cell free DNA (liquid biopsy) test test for
fetal sex and trisomies
which test detects mutations in single genes
polymerase chain reaction (PCR)
two types: next generation sequencing (NGS) and Sanger DNA sequencing
which three tests detect biochemical abnormalities associated with genotypes
sweat testing
assay of enzyme activity
hemoglobin electrophoresis
which disease is detected via sweat testing
cystic fibrosis
which disease is detected via assay of enzyme activity
pompe disease
which disease is detected via hemoglobin electrophoresis
sickle cell anemia
