Notes in 4 Genetics Basis for Disease

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Published	07/30/2024	Three approaches of {{c2::gene mapping}} discussed (i.e. approaches in discovering particular genes implicated in disease):{{c1::1. Linkage analysis (…
Published	07/30/2024	Linkage analysis is {{c1::family}}-based
Published	07/30/2024	Association analysis is {{c1::population}}-based
Published	07/30/2024	Linkage analysis can be used only if the disease of interest follows a {{c1::Mendelian inheritance}} pattern
Published	07/30/2024	Association analysis is used for studying {{c1::complex (multifactorial)}} diseases
Published	07/30/2024	Genome sequencing is used for studying {{c1::rare Mendelian}} diseases
Published	07/30/2024	What makes a Mendelian disorder rare?{{c1::1. Not enough families for linkage analysis can be secured2. Genetically lethal (i.e. poor genetic fitness)…
Published	07/30/2024	{{c1::Genome sequencing}} is best used in studying diseases that cannot be analyzed using {{c2::linkage analysis}}
Published	07/30/2024	{{c2::Linkage analysis}} tests only the {{c1::coinheritance}} of the disease with a particular genomic region, not the role of the marker in the disea…
Published	07/30/2024	Associational analysis may utilize 3 research designs:{{c1::1. Case-control studies2. Cross-sectional studies3. Cohort studies::3}}
Published	07/30/2024	Do homologous chromosomes look identical under the microscope?{{c1::Yes}}
Published	07/30/2024	{{c1::Alleles}} are alternative forms of a gene resulting from the differences at the same locus on a pair of homologous chromosomes
Published	07/30/2024	{{c1::Polymorphisms}} are multiple forms of alleles that are common or carried by approximately {{c2::2% or more}} of the {{c3::population}}
Published	07/30/2024	Based on the recombination of alleles, a gamete may be {{c1::parental (purely paternal or maternal; non-recombinant; AB, ab)}} or {{c1::nonparental (c…
Published	07/30/2024	A {{c1::polymorphic loci}} is a genetic loci with two or more alleles, at which the most common form has a frequency not exceeding {{c2::0.95}} in a g…
Published	07/30/2024	{{c1::Syntenic}} genes reside on the same {{c2::chromosome}} regardless of their distance from each other
Published	07/30/2024	The {{c1::synteny}} of genes leads to {{c2::non-recombinant}} chromosomes
Published	07/30/2024	{{c1::Recombinant (non-parental) chromosomes}} is a result of {{c2::at least one}} crossing over in the segment of the chromatids between the loci dur…
Published	07/30/2024	{{c1::Nonrecombinant (parental) chromosomes}} is a result of {{c2::no}} crossing over during meiosis
Published	07/30/2024	How many crossing overs occur between homologous chromosomes during meiosis?{{c1::1–4::range}}
Published	07/30/2024	If two syntenic loci are {{c1::sufficiently far apart}}, then RC:NRC (the ratio of recombinant chromosomes to nonrecombinant chromosomes produced…
Published	07/30/2024	A parental chromosome is said to be {{c1::nonrecombinant}}
Published	07/30/2024	A nonparental chromosome is said to be {{c1::recombinant}}
Published	07/30/2024	T/FAt least one crossing over guarantees the production of recombinant chromosomes, regardless of how many crossing overs occured thereafter{{c1::T}}
Published	07/30/2024	The {{c2::recombinantion frequencies}} (θ) of alleles fall between {{c1::0–0.5}}
Published	07/30/2024	Recombination frequency is {{c1::directly}} proportional to the distance between two alleles
Published	07/30/2024	T/FIf two loci are so close together, it can be said that they are also transmitted together all the time{{c1::T}}
Published	07/30/2024	A {{c2::smaller}} recombination frequency means {{c1::fewer}} nonparental genotypes in the offspring
Published	07/30/2024	A {{c2::higher}} recombination frequency means {{c1::more}} nonparental genotypes in the offspring
Published	07/30/2024	Two criteria must be met to perform a linkage analysis:{{c1::1. A parent must be informative (i.e. heterozygous at both alleles)2. Phase alleles must …
Published	07/30/2024	In linkage analysis, a parent is said to be "{{c1::informative}}" if the he/she is {{c2::heterozygous}} at both alleles (studied, marker)
Published	07/30/2024	{{c1::Phase}} refers to which {{c2::homologue}} an allele is located relative to a that of a different allele (e.g. disease allele and marker allele)
Published	07/30/2024	If the two alleles (e.g. disease, marker) are on the {{c1::same}} homologue, they are said to be in {{c2::coupling (cis)}}
Published	07/30/2024	If the two alleles (e.g. disease, marker) are on {{c1::different}} homologoues, they are said to be in {{c2::repulsion (trans)}}
Published	07/30/2024	{{c1::Haplotype}} is a combination of alleles found on the same chromosome that are {{c2::inherited together}}
Published	07/30/2024	A haplotype is a set of alleles that are in the {{c1::cis}} phase
Published	07/30/2024	In linkage analysis, If there is no informative parent, it is impossible to determine {{c1::whether or not recombination had occured}}
Published	07/30/2024	In linkage analysis, if the phase of informative parent is unknown, it is impossible to determine {{c1::which children are recombinant and nonrecombin…
Published	07/30/2024	{{c1::Genetic linkage}} is the departure from the independent assortment of loci
Published	07/30/2024	If RF (θ) = {{c1::0}}, two loci are said to be {{c2::completely linked}}
Published	07/30/2024	If RF (θ) = {{c1::0.5}}, two loci are said to be {{c2::unlinked}}
Published	07/30/2024	Map distance is a theortical concept based on actual data of {{c1::observed recombination (θ)}}
Published	07/30/2024	The map distance unit, centiMorgan, is named after Thomas Hunt Morgan who studied genetic recombination in the specieis {{c1::Drosophila melanoga…
Published	07/30/2024	The genome of {{c1::females}} have a greater genetic length than {{c1::males}} (males vs. females)
Published	07/30/2024	The genetic length of the genome of females is approximately {{c1::60% greater}} than males
Published	07/30/2024	A map distance of 80 cM translates to θ = {{c1::0.5}}
Published	07/30/2024	The map distance of two widely spaced loci are extrapolated from the map distance unit of an {{c1::intervening}} marker than is usually {{c2::≤ 1 cM}}…
Published	07/30/2024	The difference in the genetic length of the female and male human genome is consistent and uniform across each {{c1::autosome}}
Published	07/30/2024	What is the sex-averaged genetic length of the entire haploid human genome in map units cM?{{c1::3790 cM (ave = 1.15 cM/Mb)}}
Published	07/30/2024	Which sex have an increased recombination per unit length of DNA?{{c1::Females}}
Published	07/30/2024	What (partly) accounts for the increased recombination per unit length of DNA in females?{{c1::The years that the female gamete is arrested in me…
Published	07/30/2024	{{c1::Recombination hotspots}} are the regions within the genome where the rate, and the frequency of recombination are optimum
Published	07/30/2024	The size of recombination hotspots vary from {{c1::≤ 1000–2000}} DNA base pairs
Published	07/30/2024	While recombination hotspots account for {{c1::60%::%}} of all meiotic recombination in the human genome, it only accounts fo {{c2::6%::%}} of sequenc…
Published	07/30/2024	What is the biological basis of recombination hotspots?{{c1::still unknown}}
Published	07/30/2024	There is {{c1::linkage equilibrium}} if frequencies of the 4 positive haplotypes follow directly from the allele frequencies
Published	07/30/2024	There is {{c1::linkage disequilibrium}} if the frequency of any 1 of the haplotypes is not equal to the product of the frequencies of the individual a…
Published	07/30/2024	In a population, if a certain haplotype (e.g. S-a) always occurs and the other does not show up at all (e.g. S-A), then there is {{c1::complete}} link…
Published	07/30/2024	In a population, if a certain haplotype (e.g. S-a) occurs more frequently at the expense of another i.e. becomes less frequent (e.g. S-…
Published	07/30/2024	{{c1::Linkage disequilibrium}} refers to the non-random association of alleles at two or more loci in a general population.
Published	07/30/2024	In measuring linkage disequilibrium, the notation {{c1::D}} refers to the {{c2::deviation (δ) between the expected and actual haplotype frequencies}}
Published	07/30/2024	In measuring linkage disequilibrium, how is D computed?{{c1::}}
Published	07/30/2024	In measuring linkage disequilibrium, if D {{c1::= 0}}, then the alleles are in {{c2::linkage equilibrium}}
Published	07/30/2024	In measuring linkage disequilibrium, if D {{c1::≠ 0}}, then the alleles are in {{c2::linkage disequilibrium}}
Published	07/30/2024	To determine if LD occurs in a population (D), the frequency of {{c1::individual alleles}} and {{c1::haplotypes}} within that population must also be …
Published	07/30/2024	What constitutes a {{c1::disease-containing haplotype}}?{{c2::The polymorphic loci linked to the disease locus}}
Published	07/30/2024	The degree to which a disease-containing haplotype will persist intact over generations depends (in part) on the probability that {{c1::recombination}…
Published	07/30/2024	The speed with which recombination will move the disease allele onto a new haplotype depends on a number of factors:{{c1::1. Number of generations (i.…
Published	07/30/2024	{{c1::Positive selection}} of a haplotype results in its {{c2::overrepresentation}}
Published	07/30/2024	{{c1::Negative selection}} of a haplotype results in its {{c2::underrepresentation}}
Published	07/30/2024	An "original" disease-containing haplotype is the haplotype formed when the {{c1::disease allele first entered the population}} (e.g. {{c2::mutation}}…
Published	07/30/2024	Linkage disequilibrium is better quantified by a measure derived by D that is:{{c1::D' = D/F}}*bonus why?
Published	07/30/2024	Measuring Linkage Disequilibrium (D' = D/F)if D {{c1::>}} 0, then the correction factor (F) is equal to?{{c2::the smaller value between:1. freq(A) …
Published	07/30/2024	Measuring Linkage Disequilibrium (D' = D/F)if D {{c1::<}} 0, then the correction factor (F) is equal to?{{c2::the smaller value between:1. freq(A) …
Published	07/30/2024	{{c2::D'}} measures the linkage disequilibrium in values varying from {{c1::-1}} to {{c1::+1}}
Published	07/30/2024	If D' = {{c1::0}}, there the alleles are in {{c2::linkage equilibrium}}
Published	07/30/2024	If D' = {{c1::±1}}, the alleles are in {{c2::very strong linkage disequilibrium}}
Published	07/30/2024	{{c1::LD blocks}} are clusters of loci with alleles in {{c2::high}} linkage disequilibrium across segments of only a few kilobase pairs to a few dozen…
Published	07/30/2024	Among African, European, and Chinese and Japanese population, {{c2::Africans}} have the {{c1::smallest}} LD blocks
Published	07/30/2024	What accounts for the difference in LD block size among populations?{{c1::Number of recombination opportunities within the ancestry of populations}}
Published	07/30/2024	The boundaries between LD blocks often coincide with {{c1::meiotic recombination hot spots}}
Published	07/30/2024	In clinical medicine, a {{c2::disease state}} is defined by a collection of {{c1::phenotypic}} findings seen in a patient or group of patients
Published	07/30/2024	A disease gene is mapped to identify the {{c1::gene responsible for causing or increasing susceptibitly to disease}}
Published	07/30/2024	A disease gene is mapped to focus the attention on {{c1::a specific region of a genome}}
Published	07/30/2024	A disease gene is mapped to determine: 1. the degree of {{c1::allelic heterogeneity}},2. the {{c2::penetrance}} of different alleles3. the {{c3::freq…
Published	07/30/2024	{{c2::Linkage}} analysis relies on the computation of {{c1::likelihood ratio}}
Published	07/30/2024	In linkage analysis, the magnitude of linkage is determined by the {{c1::LOD score (Z)}}
Published	07/30/2024	What is usually the first step in identifying gene(s) responsible for causing or increasing susceptibility to disease?{{c1::Gene mapping}}
Published	07/30/2024	While both D' and LOD score (Z) measure genetic linkage...D' is based on {{c1::frequencies of alleles and haplotypes within a population}}LOD score (Z…
Published	07/30/2024	To determine if two loci are linked and how far apart they are (LOD score [Z]), the number of {{c1::individuals (N)}} and {{c1::recombinant chromosome…
Published	07/30/2024	The binomial coefficient N!/r!(N-r)! accounts for all {{c1::possible birth orders in which the recombinant and nonrecombinant children can appear in t…
Published	07/30/2024	LECTURE BASEDHow is the likelihood of data computed if loci were (un)linked at distace θ? (i.e. linkage or non-linkage probability){{c1::(θ/2)r x&nbsp…
Published	07/30/2024	{{c2::θmax}} is the best estimate of RF as it yields the {{c1::highest}} likelihood ratio
Published	07/30/2024	In Linkage Analysis, {{c1::likelihood ratios}} are usually expressed in {{c2::LOD scores (Z)}}
Published	07/30/2024	How is likelihood ratio converted to LOD score (Z)?{{c1::log10 (likelihood ratio)}}
Published	07/30/2024	In linkage analysis, a LOD score (Z) provides:1. {{c1::Best estimate of recombination frequency (θmax)}}2. {{c2::How strong evidence is for linkage at…
Published	07/30/2024	One limitation of linkage analysis done across multiple families is the possible presence {{c1::locus heterogeneity}} obscuring evidence for gene…
Published	07/30/2024	Ignoring the the binomial coefficient {N!/r!(N-r)!}, how is likelihood of data at RF (θ) computed if phase of informative parent is known?Likelihood =…
Published	07/30/2024	Ignoring the the binomial coefficient {N!/r!(N-r)!}, how is likelihood of data at RF (θ) computed if phase of informative parent is unknown?…
Published	07/30/2024	Given recombination fraction θ, what is the probability that no recombination occurs?{{c1::1-θ}}
Published	07/30/2024	Interpret: A LOD score (Z) = 3.6 at θmax = 0.06 means that two loci are {{c1::linked}} at a recombination distance of {{c2::~0.06}}
Published	07/30/2024	{{c1::Association}} analysis finds {{c2::particular alleles}} that are associated with the disease in a sample from the population
Published	07/30/2024	{{c1::Disease association}} is the comparison between presence of particular allele at a locus at increased or decreased frequency in affected individ…
Published	07/30/2024	If odds ratio {{c1::=}} 1, there is no association between the exposure and odds of outcome
Published	07/30/2024	If odds ratio {{c1::>}} 1, exposure is associated with higher odds of outcome
Published	07/30/2024	If odds ratio {{c1::<}} 1, exposure is associated with lower odds of outcome
Published	07/30/2024	{{c2::Odds ratio}} measures the association of between {{c1::exposure}} and the higher/lower {{c1::odds of outcome}}
Published	07/30/2024	{{c2::Relative risk}} measures the association of between {{c1::exposure}} and the higher/lower {{c1::disease outcome}}
Published	07/30/2024	{{c1::Risk ratio in relatives (λ)}} is the {{c2::prevalance}} of a particular disease phenotype in an in an {{c3::individual's relatives}} v…
Published	07/30/2024	Explain why OR is a good approximation for RR in rare diseases? i.e. RR ≈ OR{{c1::when a < b and c < d, (a + b) ≈ b and (c + d) ≈ d}}
Published	07/30/2024	The significance of any association is assessed by what statistical test?{{c1::Chi-square test}}
Published	07/30/2024	The magnitude of association is given by {{c1::how far from 1}} RR or OR is
Published	07/30/2024	Interpret: An odds ratio (OR) = 6.9 with 95% confidence interval of 2.3–20.6 means that there is {{c1::6.9 times greater}} odds of having the dis…
Published	07/30/2024	Interpret: A relative risk (RR) = 2.6 with 95% confidence interval of 1.3–5.1 means that there is a {{c1::moderately increased}} risk of having the di…
Published	07/30/2024	Should samples be related in association analyses?{{c1::No}}
Published	07/30/2024	One limitation of association analysis is the false-positive association caused by {{c1::population stratification}} if the frequencies of alleles bet…
Published	07/30/2024	{{c1::Population stratification}} refers to the systematic differences in {{c2::allele frequencies}} between cases and controls as a result of {{…
Published	07/30/2024	{{c1::Ancestry informative}} markers are alleles that show large allele frequencyamong populations originating in different parts of the world
Published	07/30/2024	{{c1::Copy number variation (CNV)}} is a genetic phenomenon in which the number of copies of a particular {{c2::gene}} varies…
Published	07/30/2024	One limitation of association analysis is the false-positive association caused by inappropriate {{c1::mutliple hypothesis testing…
Published	07/30/2024	A genome-wide association study (GWAS) usually include a {{c1::replication study}} in a different completely independent group to account for possible…
Published	07/30/2024	Does association analysis provide evidence behind the functional role of a polymorphic marker in a disease? {{c1::No but can usually pinpoin…
Published	07/30/2024	Comparison of Linkage analysis and Association Analysis: no answer {{c1:::)}}
Published	07/30/2024	SNPs are {{c1::synonymous}} if they code for the same amino acid
Published	07/30/2024	Genome-wide association studies are usually presented graphically using a {{c1::Manhattan plot}}
Published	07/30/2024	{{c1::Effect size}} is a measure of the strength of an {{c2::association}} between two variables (e.g. OR, RR)
Published	07/30/2024	A whole-exome sequence (WES) sequencues approximately {{c1::2}}% of the genome
Published	07/30/2024	{{c2::Whole genome sequencing}} involves the application of a {{c1::variant filtering scheme}} to narrow down the list of possible responsible gene va…
Published	07/30/2024	1. Location with respect to protein-coding genes2. Population frequency3. Deleterious nature of the mutation4. Consistency with likely inher…
Published	07/30/2024	Variant filtering scheme in GWS (keep or discard)variants that are within or near exons of protein-coding genes{{c1::keep::keep or discard}}
Published	07/30/2024	Variant filtering scheme in GWS (keep or discard)variants that are within introns or intergenic regions{{c1::discard::keep or discard}}
Published	07/30/2024	Variant filtering scheme in GWS (keep or discard)rare variants{{c1::keep::keep or discard}}
Published	07/30/2024	Variant filtering scheme in GWS (keep or discard)Common variants (allele frequencies > 0.05){{c1::Discard::keep or discard}}
Published	07/30/2024	Variant filtering scheme in GWS (keep or discard)causes nonsyonymous mutations{{c1::Keep::keep or discard}}
Published	07/30/2024	Variant filtering scheme in GWS (keep or discard)frameshift mutations{{c1::Keep::keep or discard}}
Published	07/30/2024	Variant filtering scheme in GWS (keep or discard)alteration of highly conserved splice sites{{c1::Keep::keep or discard}}
Published	07/30/2024	Variant filtering scheme in GWS (keep or discard)Synonymous mutations{{c1::Discard::keep or discard}}
Published	07/30/2024	In GWS, if the disease is suspected to be {{c1::autosomal recessive,}} keep any variants kept from the previous steps that are {{c2::found in both cop…
Published	07/30/2024	{{c1::Ccompound heterozygosity}} is the condition of having two or more heterogeneous recessive alleles at a particular locus that can cause gene…
Published	07/30/2024	In GWS, to confirm that the disease is indeed autosomal recessive, then the (unaffected) parents must be {{c1::heterozygous}} for the variants
Published	07/30/2024	(In GWS), if the disease is suspected to be autosomal recessive and {{c1::consanguinity}} is known, the child must be a {{c2::true homozygote}} for th…
Published	07/30/2024	In GWS, if the disease is suspected to be {{c1::a new mutation}}, keep any variants kept from the previous steps that are {{c2::de novo changes in chi…
Published	07/30/2024	After variants are filtered down to a manageable number, they are further asssesed by1. {{c1::investigating if the variant makes biological sense}}*2.…
Published	07/30/2024	In cases where the gene responsible disease may turn out to be entirely unanticipated*, assesment of the variant requires the extensive use of {{c1::p…
Published	07/30/2024	GWS has a success rate of {{c1::25% to 40%::range}} in identifying a causative mutation
Published	07/30/2024	GWS may miss some mutations like {{c1::deletions}}, {{c2::copy number variations}}, {{c3::non-coding mutations}} and {{c3::regulatory mutations}}
Published	07/30/2024	{{c1::Postaxial acrofacial dysostosis (Miller syndrome)}} is a rare genetic disorder characterized by {{c2::craniofacial}} malformations occurrin…
Published	07/30/2024	POAD or Miller Syndrome manifests with {{c1::frontal bossing}} where frontral area the head is prominent
Published	07/30/2024	POAD or Miller Syndrome manifests with {{c1::lower lid ectropion}} which leads totearing, dryness and corneal scarring
Published	07/30/2024	POAD or Miller Syndrome manifests with {{c1::micrognathia}} or very small lower jaw
Published	07/30/2024	POAD or Miller Syndrome manifests with {{c1::hypoplastic}} scrotum
Published	07/30/2024	POAD or Miller Syndrome manifests with {{c1::syndactyly}} wherein two or more digits are fused together
Published	07/30/2024	POAD or Miller Syndrome manifests with {{c1::synostosis}} of the {{c2::radius and ulna}}
Published	07/30/2024	POAD or Miller Syndrome manifests with {{c1::gastric dilatation}} due to twisted intestines
Published	07/30/2024	POAD or Miller Syndrome manifests with {{c1::hydronephrosis}} due to vesicoureteral reflux
Published	07/30/2024	1 of the 4 genes confimed to be mutated ni Miller Syndrome (POAD) is the {{c1::DHODH}} gene that encodes for {{c2::dihydroorate dehydrogenase}}
Published	07/30/2024	{{c1::Dihydroorotate dehydrogenase}} is a {{c2::mitochondrial}} enzyme involved in biosynthesis of {{c3::pyrimidines (C,U,T)}}
Published	07/30/2024	Genome sequencing involves the sequencing of the {{c1::affected individual}} and {{c1::his/her parents}} (who?)
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