lectures 35 & 36 Flashcards
genetic diseases (11 cards)
Explain the differences between monogenic and polygenic traits.
Monogenic:
- only one pair of genes is involved
- also called single-gene traits; follows Mendel’s law
- ex: dimples, widow’s peak
Polygenic:
- many genes are involved; traits have Gaussian distributions
- the contribution of each gene to the traits may vary
- ex: height, skin coloe
Describe how variants occur.
inherited (hereditary):
- passed from parent to child
- present throughout a person’s life in almost every cell in the body
- present in sperm and egg cells
non-inherited:
- occur at some time during a person’s life
- not in every cell in the body
- somatic variants occur in somatic cells (not sperm/egg cells)
- not passed to children
- can be caused by environmental factors or an error in DNA replication
new (de novo) variants:
- found in a child but not in either parent
- may pass to his or her child
- may occur in a parent’s egg or sperm cell but not in any of their other cells or in the fertilized egg shortly after fertilization
- variants acquired during development can lead to mosaicism
Describe how silent mutations, missense mutations, nonsense mutations, insertions, and deletions impact protein function or expression.
silent mutations- no change in the amino acid sequence
missense mutations- change in amino acid sequence
nonsense mutations- addition of a stop codon
insertions and deletions:
- multiple of three bases= insertions or deletions of one or more amino acids
- not a multiple of three bases= frameshift
Distinguish loss of function, gain of function, and dominant negative phenotypes.
complete loss of function- no expression, mutated protein with no activity
partial loss of function- reduced expression, mutated protein with reduced expression
gain of function- mutated proteins with abnormal activity (ex. oncogenes)
dominant negative- inhibition of the activity of the un-mutated protein expressed from the normal allele
Explain the molecular basis of dominant and recessive phenotypes.
dominant: Dd, DD
recessive: dd
Distinguish autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial genetic disorders from inheritance patterns.
dominant disorders:
- 50% chance of passing the trait to each child
- same probability for male and female children
- unaffected relatives or siblings do not transmit the disorder
- in many cases, the age of onset is delayed
- represented by a capital letter
- ex: Huntington’s disease, Marfan syndrome
recessive disorders:
- if both parents are carriers, 25%:50%:25% chance of having DD:Dd:dd child
- same probability for male and female children
- unaffected siblings may be carriers
- all children of an affected parent are carriers
- age of onset is frequently early in life for many children
- symptoms tend to be more uniform than with dominant disorders
- ex: phenylketonuria, Tay-Sachs disease, and all inborn errors of metabolism
X-linked dominant:
- frequently embryonic lethal for males (XY) and for homozygous mutant females (xx)
- if mother is affected (Xx): both sons and daughters have 50% chance of being affected
- if father is affected (XY): daughters are 100% affected and sons are 100% normal
X-linked recessive:
- female Xx are unaffected carriers
- all xY males are affected
- if the mother is a carrier: daughters are 50% normal and 50% carriers; sons are 50% normal and 50% affected
- if father is affected: daughters are 100% carriers, sons are 100% normal
mitochondrial genetic disorders:
- mitochondria contain their own DNA (mtDNA); circular chromosome with 37 genes inherited only from the mother
- cells contain many mitochondria which have a mixture of normal and mutant DNA (heteroplasmy)
- the severity of the disorder depends on the proportion of the mitochondria that carry the mutated gene
- affect organs that depend most on oxidative phosphorylation (skeletal muscle, heart, brain)
Predict the chances of non-carrier, carrier, and affected children of genetic disorders based on genotypes of the parents and the type of disorders.
punnet squares
DD x DD:
100% DD
DD x Dd:
50% DD and 50% Dd
DD x dd:
100% Dd
Dd x Dd:
25% DD, 50% Dd, and 25% dd
Dd x dd:
50% Dd and 50% dd
dd x dd:
100% dd
Explain the concepts of penetrance and expressivity.
penetrance:
- the percentage of individuals with a particular genotype (or gene mutation) who express the associated phenotype (or symptoms of a disorder)
- complete = 100%, incolplete = < 100% (reduced penetrance)
- influences by genetic, environmental, and lifestyle factors, many of which are unknown
expressivity:
- the degree to which a genotype (or gene mutation) is expressed as a phenotype (or symptoms of a disorder) with an individual with the genotype
- some may have relatively mild symptoms of a conditions, while others are debilitating (variable expressivity)
- influenced by other genes, epigenetics, environmental factors, etc.
Explain the mechanisms that give rise to abnormalities in the chromosome number.
abnormal number of chromosomes = having more or less than 46
occurs due to unbalances segregation of chromosomes during meiosis (nondisjunction- produces germ cells with 22 or 24 chromosomes)
fertilization of gametes with aneuploidy:
- defects associated with monosomy of the autosomes are severe and often cause miscarriage in utero
- trisomy 13 and trisomy 18 are much more severe than trisomy 21 and rarely survive beyond the first year
mosaicism:
- caused by nondisjunction occurring in the early stages of development
- part of the cells in the body have abnormal number of chromosomes
- relatively mild symptoms compared to full trisomy or monosomy
prenatal testing:
- amniocentesis
- prenatal cell-free DNA (cfDNA) screening
Identify the genetic disorders occurred by abnormalities in the chromosome number.
down syndrome (trisomy 21)
turner syndrome (monosomy X)
klinefelter syndrome (XXY or XXXY)
Explain how imprinting affects the inheritance patterns of genetic disorders.
- some regions of DNA are turned off in the copy received from mother or father
- epigenetic process that involved DNA methylation and modification; about 200 imprinted genes known in humans, only one copy is functional
- occurs in gametes and is then stably transmitted to all somatic cells derived from the zygote
- if a gene is turned off in the maternal copy and mutated in the paternal copy, none of the copies will produce a functional protein
example:
- A has a mutated allele, which is turned off during spermatogenesis
- none of A’s children (B) are affected
- the mutated allele is turned on during oogenesis in B
- all of B’s children who inherit the mutant allele (D) are affected
- all of D’s children who inherit the mutant allele will be affected
