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44 Cards in this Set
- Front
- Back
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... means that a predisposition is determined by genes
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genetic
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... means that a disorder is present at birth, may or may not be genetic in nature
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congenital
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What are these?
Single gene disorders Mitochondrial inheritance Multifactorial traits Chromosomal or cytogenetic abnormalities Diseases of unknown etiology |
categories of human genetic diseases
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what is this?
-study of inheritance of single-gene traits or disorders -assumption that traits being studied were determined by unit characters (alleles) -based on two principles: Law of Segregation and Law of Independent Assortment |
Mendelian (unifactorial) Inheritance
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What is this?
-alleles segregate into different gametes and are NEVER found in the same gamete -based on the segregation of chromosome in meiosis |
Law of segregation
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Mendelian Inheritance - law of segregation
During gametogenesis, each allele of the allelic pair separates from the other resulting in ... |
gametes with only a single copy of each gene
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what is this?
alleles for different traits, traits controlled by genes on different chromosomes assort independently based on the fact that chromosomes align along the metaphase plate independently during meiosis I, - equal chance of the maternal or paternal homolog segregating to either pole Example -Chromosome 1 has a gene with the alleles S and s -Chromosome 2 has a gene with the alleles Y and y -The following combinations are possible S and Y, S and y, s and Y, s and y. -There is no preference for one combination or the other, remember alignment was random. |
Law of Independent Assortment
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Mendelian Inheritance - law of independent assortment
During gametogenesis, segregation of the alleles of one allelic pair is ... |
independent of the alleles of another allelic pair
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what is this?
-simple method for the depiction of genotypes various mating -prediction of genotypic ratios in the offspring |
punnett square
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punnett square
One gamete comes from each ... to produce the ... of the zygote (offspring). Example: Both father and mother heterozygous for an autosomal dominant gene, with the allele A being the mutant dominant allele, and allele a being the recessive normal allele. Father and mother produce two types of gametes A and a. The possible outcomes are 25% AA (homozygous dominant), 50% Aa (heterozygous dominant), 25% aa (homozygous recessive). Ratio of ... |
parent
genotype 1:2:1 |
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Pedigree
First step in establishing a pattern of transmission is obtaining information about ... of the patient (proband) or consultand (individual requesting genetic consultation) and summarize in a pedigree. |
family history
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Standards for construction of pedigrees:
males represented by ... symbols, females represented by ... symbols line drawn between a square and a circle represents a ... between that male and female -square should be placed to the ... of the circle when possible two lines drawn between a square and a circle indicate a consanguineous mating -individuals ..., usually second cousins or closer generations connected by vertical extending down from mating line to next generation children of a mating connected by a horizontal line (... line) -children of sibship are listed in order of birth, oldest on ... normal individual represented by ... symbol, affected individual represented by ... symbol NOTE****To simplify a pedigree only one parent is shown, other omitted (parent is genotypically homozygous normal for trait) |
square
circle mating left related sibship left open solid |
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Pedigree Numbering:
Each generation labeled to left of sibship line with ... Each individual in a generation is numbered sequentially with Arabic numerals, starting at the ... |
Roman numerals
left |
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Remember! Single-gene disorders are:
-determined by alleles at a ... -characterized by patterns of ... in families -exhibit single gene ... or Mendelian inheritance |
single locus
transmission unifactorial |
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Important to analyze whether or not a genetic disorder is actually inherited as a ...
Many are found to be genetically ... (same or similar phenotypes produced by different genetic mechanisms). |
single gene disorder
heterogeneous |
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What is this?
Example is Cystic Fibrosis -autosomal recessive disorder of the epithelial ion transport -mutations in the CF transmembrane conductance regulator (CFTR) gene ->1000 different mutations and variants described across the CFTR gene |
Allelic heterogeneity
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what is this?
Example is Cutis Laxa -disorder of the elasticity of the skin -various patterns of inheritance: autosomal dominant, autosomal recessive, X-linked recessive -mutations observed in elastin, fibulin and lysyl oxidase; all lead to same phenotype |
Locus heterogeneity
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what is this?
Examples are different mutations found in the β-globin gene -development of different forms of β-thalassemias as well as sickle cell anemia |
Phenotypic or clinical heterogeneity
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... heterogeneity
-In a population, number of different mutant alleles at a single locus -In an individual, manifestation of same/similar phenotype caused by different mutant alleles ... heterogeneity -Production of identical phenotypes by mutations at two or more different loci ... or ... heterogeneity -Occurrence of clinically different phenotypes from mutations in the same gene |
Allelic
Locus Phenotypic clinical |
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Autosomal dominant
1. Phenotype appears in every generation Exceptions: A. ... mutation in gamete of phenotypically normal parent B. ... or ... of phenotype 2. Any child of an affected parent has ... chance of inheriting trait Remember! Each family member is the result of an “independent event” therefore observed deviation from 1:1 ratio can occur 3. Children that are normal do not transmit phenotype to children 4. Males and females are equally likely to transmit phenotype to children of either ... 5. Significant proportion due to new mutations 6. Most mutations impact gene that code for structural proteins rather than ... |
De novo
Non-penetrance subtle expression 50% sex enzymes |
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Autosomal Recessive (Mating of Aa X Aa)
1. If the phenotype appears in more than one member of the kindred, it is most likely seen in a sibling of the ... 2. In most disorders, males and females affected ... 3. Parents of affected child are ... carriers (heterozygotes) of mutant alleles. 4. Parents of affected child may be ...; likely is mutant allele is rare the population -consanguineous means relation by descent from a common ancestor -in genetic terms, it is a union of individuals related to each other close or closer than second cousins -NOT a common explanation for autosomal recessive disorders 5. Recurrence rate of disorders is #% for each sibling. Other matings include -Aa X aa; 50% offspring affected, 50% offspring unaffected -aa X aa; 100% offspring affected |
proband
equally asymptomatic consanguineous 25 |
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what is this?
-typically expressed in males who receive mutant allele (hemizygous) -only in females who are homozygous for mutant |
X-linked recessive
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X-linked recessive
1. Incidence MUCH higher in ... than ... 2. Heterozygous females typically ..., may express severe form of condition if chromosome expressing normal allele undergoes X-inactivation 3. Affected male transmits mutant allele to all his daughter (...); daughters have a 50% chance of passing the mutant allele onto their sons 4. Mutant allele is normally not transmitted from father to son, rather passed from affected male to all his ... 5. Isolated cases due to de novo mutations. |
males
females unaffected obligate carrier daughters |
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X-linked recessive Matings
1. Affected male (XhY) and normal female (XX) -all daughters ... -all sons ... 2. Normal male (XY) and carrier female (XhX) -daughters: #% normal, #% carriers - sons: #% normal, #% affected 3. Affected male (XhY) and carrier female (XhX) - daughters: 50% affected, 50% carriers - sons: 50% normal, 50% affected |
carriers
unaffected 50 50 50 50 |
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X-linked Dominant
-regularly expressed in ... 1. Mating of an affected male with a normal female -... affected sons -... daughters affected 2. Male and female offspring of affected females have #% chance of inheriting mutant allele -see a similar pattern as in autosomal dominant 3. Affected females are twice as common as affected males; females exhibit milder expression |
heterozygotes
no all 50 |
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Some forms of X-linked dominant disorders are lethal in males and expressed exclusively in females
-lethality in males occurs before ... -transmission by affected females producing affected females, normal females and normal females in equal proportions (1:1:1) |
birth
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Characteristics of mtDNA
-... DNA located inside mitochondria -37 genes: 22 tRNAs, 2 rRNAs and 13 that encode for protein subunits of oxidative phosphorylation complex -remaining mitochondrial proteins encoded by genomic DNA including the other 74 proteins of the ... |
-circular
-oxidative phosphorylation complex |
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Mitochondrial DNA (mtDNA) mutations:
-mutations in mtDNA inherited ... or acquired as somatic mutations -diseases of the oxidative phosphorylation complex arise from mutations in mtDNA as well as genomic DNA |
maternally
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Patterns of inheritance due to unique features of mitochondrial chromosomes:
1. ... - multiple copies of mtDNA per mitochondria replicate and sort randomly among newly synthesized mitochondria and in turn are randomly distributed between the daughter cells 2. Homoplasmy and heteroplasmy -Homoplasmy is when a cell contains a ... population of either normal mtDNA or mutant mtDNA -Heteroplasmy is when a cell contains a ... population of normal and mutant mtDNA 3. Maternal inheritance -mtDNA is always inherited entirely from the ... -... mitochondria generally eliminated from embryo |
Replicative segregation
pure mixed mother sperm |
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... -cell contains a mixed population of normal and mutant mtDNA
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Heteroplasmy
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...- cell contains a pure population of either normal mtDNA or mutant mtDNA
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Homoplasmy
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Mitochondrial inheritance
1. Females ... for mutation will pass mutation onto all children; children of males carrying similar mutation will not Remember! Mitochondria from sperm normally eliminated from embryo 2. Females ... for mutation will pass mutation on to all children; risk and severity of disease varies depending on fraction of mutant mitochondria 3. In a ... individual, fraction of mutant mitochondria vary in the different tissues causing a spectrum of disease among family members -... and variable expression |
homoplasmic
heteroplasmic heteroplasmic pleiotropy |
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... Inheritance
referred to as such because genetic and environmental factors contribute to the manifestation of disease -many times genetic cause unknown environmental factors interact with multiple genes (polygenes) generating a susceptibility distribution -individuals who lie at the wrong extreme end of the distribution curve are affected |
Multifactorial
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Multifactorial inheritance
Disorders include common ... malformations such as cleft lip/palate and congenital heart defect and acquired diseases of childhood/adulthood such as asthma, autism hypertension, Parkinson disease and several psychological disorders (depression, bipolar disorder and schizophrenia). |
congenital
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Multifactorial inheritance
-Disorders that ... but do not show patterns of unifactorial or Mendelian inheritance -Multiple genes (polygenic) involved in expression of trait -Genes do not act in a dominant or recessive manner -Genes act in concert, each adds/detracts a small amount (... effect) -... factors interact with the genotype to produce final phenotype -Observe a normal (continuous) distribution (... curve) as observed with polygenic traits |
“run” in a family
cumulative Environmental bell-shaped |
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... or ... inheritance:
many human characteristics are inherited polygenically -height, intelligence, skin color, blood pressure, etc. |
Polygenic
quantitative |
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Polygenic traits show ... (continuous) distribution
-extremes of a trait are found at the ... of the distribution curve. |
normal
ends |
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Most offspring display polygenic traits tend to fall more towards the population mean rather than toward the mean of their parents’ mean- “...”
Simple example- two individuals with genius IQ produce offspring of normal intelligence |
Regression to the mean
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Polygenic (quantitative) inheritance)
-Inheritance and expression of a phenotype determined by many genes at different loci -Each gene exerts a small effect; effects of genes are ... |
cumulative
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Remember! Multifactorial traits, like polygenic traits, show normal (...) distribution.
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continuous
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So when does the fine line between normal expression of multifactorial traits and disease state occur?
Take two concepts into account: 1. ... -causative factors (‘bad genes’ and adverse environmental factors) -not measurable, only derive means from the incidence of disease 2. ... -point at which normal development ceases and disease state begins |
Liability
Threshold |
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When does disease occur in an individual? (must look at normal distribution of population)
-as the number of multifactorial genes for a trait increases, the ... for a disease increases. -when the ... point is reached, the liability is so great that disease results. -the critical difference between liability is the .... In relatives? -curve will be shifted to the ... -shift dependent of distance of ... to affected individual At any point beyond the threshold, ... results. Below threshold, normal development. |
liability
threshold threshold right relation disease |
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Hallmarks of Multifactorial inheritance:
-Most affected children have ... parents; true of diseases and quantitative traits. -The presence of more than one affected relative ... the risk for other relatives. -... increases with severity of disease; more severely affected parent produces more likely to have an affected child |
normal
increases Recurrence risk |
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Hallmarks of Multifactorial Inheritance:
-... of most severely affected patients have highest incidence of condition. -Risk is greatest among close relatives of ... and decreases rapidly in more ... relatives. -If the two sexes have a different probability of being affected, the least likely sex, if affected, is the most likely sex to produce ... |
Relatives
proband distant an affected offspring |
