Q2-FUN18+19/Mendelian Genetics I and II Flashcards
most cells are ________ ploid
diploid
what does it mean that diploid cells are homologous?
we have 2 homologous copies of each chromosome
2 copies of each gene, 1 per chromosome copy (maternal + paternal)
each gene copy is called an ______
allele
alleles can _________ in their DNA base seq. so an individual can have diff alleles of a gene ( A and a)
vary slightly
what are the mendelian inheritance patterns?
autosomal dominant/recessive
Y-linked
X-linked dominant/recessive
What does this mean in a pedigree?
male, female, sex unknown
What do these mean in a pedigree?
What do these mean in a pedigree?
how many autosomal dominant traits have been found so far?
over 1000
auto. dom. traits are expressed at ________zygous
heterozygous (Aa)
most cases of auto. dom. disease will be ______
heterozygous
what is the range of auto. dom. disorders?
they can die before maturity or have late onset diseases (wide range)
dom. homozygotes are at a ________ relative to heterozygotes and frequently die before reproductive maturity
selective disadvantage
auto. dom. allel frequencies are usually high/low
low
What are some types of auto. dom. disease? (4)
familial hypercholesterolaemia, polycystic kidney disease, familial adenomatous polyposis (FAP), neurofibromatosis
what is familial hypercholesterolaemia?
genetic disorder, caused by defect in chromosome 19, that makes the body unable to remove LDL cholesterol from the blood which results in people who are 30-40 years old be at high risk of myocardial infarction
1/______ people have a het mutation for familial hypercholesterolaemia and their plama LDL levels are ___x as much as a normal.
500, 2
1/______ people have a homo mutation for familial hypercholesterolaemia and their plama LDL levels are ___x as much as a normal.
1M, 10
what happens to people that have homozygous familial hypercholesterolaemia?
fatal myocardial infarctions in childhood/adolescence.
what is polycystic kidney disease?
many cysts grow in kidney, and these cysts fill w/ fluid. if there are too many or they get too big, kidneys become damaged.
What is familial adenomatous polyposis (FAP)?
cancer develops in colon and rectum
What is neurofibromatosis?
tumors form on nerve tissues
What is the characteristic pattern of auto dom inheritance?
vertical, disease is passed from one generation to the next and each affected person has an affected parent
which has a larger probably of being affected by auto. dom.?
male and female are equal
if affected, males/females/both will transmit the mutation if it is auto dom
both
approx ___% of the offspring of an auto dom affected parent will be affected
50
What may cause exceptions to the auto dom pattern?
mutations, variable expressivity, and reduced penetrance
how is a mutation an exception to the auto dom inheritance pattern?
random cases may arise within families by de novo mutation which causes auto dom traits to not be expressed
how is variable expressivity an exception to the auto dom inheritance pattern?
everyone with the genotype shows it, it just varies from person to person how severely the phenotype is expressed
how is reduced penetrance an exception to the auto dom inheritance pattern?
some people have the genotype but dont express the phenotype
What is haploinsufficiency?
This occurs when one copy of a gene is inactivated/deleted and the other copy of the gene isn’t strong enough to produce the needed product to keep normal function.
What is dominant negative effect?
Dominant-negative effects occur when cells express mutant proteins that impair the activity of the cells’ usually-made functional counterpart.
how can a gain-of-function mutation at a single gene cause a disease phenotype?
the function of a mutant protein is enhanced
ex. achrondroplasia, huntingtons disease
how does a loss of heterozygosity cause a disease phenotype?
inhertied copy of mutant gene and random loss of normal allele, even in only a few cells, renders those cells cancerous
symptoms of auto rec diseases are only seen in _________
recessive homozygotes (2 mutant alleles and no normal allele)
heterozygotes are said to be _______ of a mutation if auto rec
carriers
auto rec is more/less common than auto dom
more
most common auto dom mating type?
most common auto rec mating type?
what are some ways to identify auto rec diseases?
newborn screening programs, multiple affected siblings within large sib-ships, parental consanguinity, demonstration of partial defect in obligate heterozygotes
identifying auto rec diseases can be complicated by _____ and _____
de novo mutation and genetic heterogeneity
What is genetic heterogeneity?
Genetic heterogeneity can be defined as mutations at 2+ genetic loci that produce the same or similar phenotypes
What are the 2 types of genetic heterogeneity?
allelic geterogeneity and locus heterogeneity
what is the diff b/w allelic and locus heterogeneity?
explain mutation nomenclature.
What is allelic heterogeneity?
What is locus heterogeneity?
Males are ________ for the X chromosome
hemizygous
What is lyonization?
X chromosome inactivation
in female cells, one of the two ____ chromosomes is inactivated
X chromosomes
inactivation occurs when?
early in embryonic life
inactivation is _________
random, either the paternal/maternal X may be inactivated
inactivation is permanent and ______ propagated
clonally
inactivation is virtually ________
complete
the inactive X appears as a dark-staining mass known as a _________
Barr-body
What is a Barr body?
condensed heterochromatic chromosome
x linked diseases may be ______ or ________
rec or dom
X linked mutant genes are ____ expressed in males
fully
X linked traits are _______ expressed in females
variably
What does intermediate effect mean regarding X linked diseases?
clinically unaffected but biochemically abnormal
What is skewed X inactivation?
normal phenotype
more than random X chromosomes containing the MUTANT gene are inactivated
occurs when the X-inactivation of one X chromosome is favored over the other, leading to an uneven number of cells with each chromosome inactivated
what is manifesting heterozygote?
clinically affected
more than random X chromosomes containing the Normal gene are inactivated
A female heterozygous for a sex-linked recessive mutant gene who expresses the same phenotype as a male hemizygous for the mutation. This rare phenomenon results from the situation where, by chance, most somatic cells critical to the expression of the mutant phenotype contain an inactivated X chromosome carrying the normal allele of the gene.
An X-linked disease may or may not be expressed clinically in a _______________
heterozygous female
diseases which are rarely expressed clinically in females are said to be ___________
X-linked recessive (most known X-linked diseases are X-linked rec)
diseases which are expressed clinically in many females are said to be _____________
diseases are characterized as XLR vs XLD depending on _________________
the relative proportions of females who are affected
Describe and X linked recessive pedigree.
What are 2 types of XLR diseases?
hemophilia A and Duchenne muscular dystrophy
What is hemophilia A?
incidence is 1/5000-10000
deficiency in factor VIII
soft tissue bleeding in joints
What is Duchenne Muscular dystrophy?
incidence is 1/3300
form of muscular dystrophy
onset at approx 5 years old
progressive muscle weakness
death due to resp/card complications in 20’s
what is Hypophosphatemic rickets?
condition where the bones become painfully soft and bend easily
typically, expression of XLD symptoms is more severe and constant in _____ than in ______
males, females
What is extranuclear inheritance?
transmission of genes that occur outside of the nucleus (mitochondria)
What is mtDNA?
the mitochondria has a small circular DNA genome (abt 16kbp long)
mtDNA is maternally transmitted via the ______
ovum
certain human diseases characterized by abnormal mitochondria often involve ________ and _____ muscle impairment and neurological problems
skeletal, cardiac
What is the difference between homoplasmy and heteroplasmy?
Homoplasmy refers to the state of having uniformly normal or abnormal mitochondria in a tissue, while heteroplasmy refers to the state of having a mixture of normal and abnormal mitochondria in a tissue.
What is the difference between normal, premutation, and mutation triplet repeat disorders?
triplet repeat disorders may be classified as _____, _______, or ________ inheritance
dominant, recessive, X-linked
What does unstable expansion mean?
variation
