Genetics in Human and Animal Medicine Flashcards
(297 cards)
1
Q
what is a karyotype?
A
the set of chromosomes found in a particular species
2
Q
what is a diploid karyotype?
A
having 2 copies of each chromosomes
3
Q
what are the 2 types of chromosomes?
A
autosomes and sex chromosomes
4
Q
what are autosomes?
A
chromosomes which are diploid in all individuals of a species regardless of sex
5
Q
what are sex chromosomes?
A
chromosomes which confer sexual traits and are different between males and females
6
Q
which are the heterogametic sex in mammals?
A
males
7
Q
what is the heterogametic sex?
A
the sex with 2 different types of sex chromosomes
8
Q
how many chromosomes do humans have?
A
22 pairs of autosomes, 1 pair of sex chromosome
9
Q
how many chromosomes do dogs have?
A
38 pairs of autosomes and 1 set of sex chromosomes
10
Q
what are centromeres the site of?
A
spindle attachment during mitosis and constriction between the 2 sister chromatids in G2 cells
11
Q
what are sister chromatids?
A
the 2 replicated chromosomes present in G2 of the cell cycle
12
Q
what is a chromosomal arm?
A
the region from the centromere to the end of the telomere
13
Q
which is the p-arm?
A
the shorter of the 2 chromosome arms
14
Q
which is the q-arm?
A
the longer of the 2 chromosome arms
15
Q
what percentage of the genome is non-coding?
A
98%
16
Q
what does non-coding mean?
A
doesn’t encode protein-coding gene exons
17
Q
what is the reference genome?
A
a completely sequenced genome isolate that is used for reference for genetic studies
18
Q
how many chromosomes and chromatids will a human cell in G1 have?
A
46 chromosomes, 46 chromatids
19
Q
how many chromosomes and chromatids will a human cell in G2 have?
A
46 chromosomes and 92 chromatids
20
Q
what is a locus?
A
a position in a genome
21
Q
what are alleles?
A
variant sequences at a particular locus
22
Q
when are 2 loci considered linked/under linkage disequilibrium?
A
if they are frequently inherited together
23
Q
what are the 5 classes of genome variation?
A
SNVs, indels, structural variants, transposable element insertions, cytogenetic variation
24
Q
what are SNVs?
A
single nucleotide variations
25
what are indels?
small insertions and deletions
26
what are SNVs also known as?
point mutations or substitutions
27
when are SNVs termed SNPs?
if they occur in the germline and are variable within individuals in a population
28
what are SNPs?
single nucleotide polymorphisms
29
what are the 6 types of SNV?
2 transitions and 4 transversions
30
what do transitions involve?
only purines/pyrimidines respectively
31
what do transversions involve?
purines -> pyrimidines or vice versa
32
what 3 cellular DNA repair pathways repair the majority of incipient SNVs?
NER, BER, MMR
33
what is NER?
nucleotide excision repair
34
what is BER?
base excision repair
35
what is MMR?
mismatch repair
36
what does NER primarily repair?
helix distorting damage
37
what does BER primarily repair?
small, non-helix-distorting lesions
38
what does MMR repair?
base-base mismatches
39
what can SNVs be caused by?
exogenous or endogenous mutational processes
40
what are exogenous mutational processes?
those that involve exposure to exogenous agents
41
what are endogenous mutational processes?
processes that derive from mutational activities that naturally operate within the cell
42
what mutation is present in 60% of human malignant melanomas?
BRAF V600E
43
what does the BRAF V600E mutation cause?
activation of the cell cycle without growth factor binding to RTK
44
SNV mutation in what gene causes phenylketonuria?
PAH, the gene encoding phenylalanine hydroxylase
45
what causes xeroderma pigmentosum?
mutations, often SNVs, in components of the NER pathway causing extreme sensitivity to UV light and accumulation of SNVs in sun-exposed cells
46
where does polymerase slippage often occur?
at simple repeat tracts called microsatellite/STRs
47
what does polymerase slippage cause?
indels
48
what are STRs?
short tandem repeats
49
what are microsatellite length alleles?
alleles present at simple repeat tracts characterised by different lengths of repeat tract loci
50
what is the causative mutation in trinucleotide expansion diseases?
simple repeat indels
51
what sort of disease is Huntington's?
trinucleotide expansion disease
52
do all indels occur at repeat regions?
no
53
what do structural variants in DNA often involve?
dsDNA breakage repaired by HR or NHEJ
54
what are structural variants in DNA?
large scale genomic rearrangements that lead to juxtaposition of DNA that wasn't previously connected
55
what are the 2 types of structural variants?
interchromosomal or intrachromosomal
56
what is involved in inter-chromosomal structural variants?
2 chromosomes
57
what is involved in intrachromosomal structural variants?
different parts of the same chromosome
58
what are balanced structural variants?
ones that don't lead to an overall gain or loss of DNA from the cell
59
what are unbalanced structural variants?
ones that introduce additional DNA or cause DNA to be lost from the cell leading to copy number variants
60
what is the Philadelphia chromosome?
a translocation between human chromosomes 9 and 22, type of balanced structural variant
61
what disease is the Philadelphia chromosome frequently observed in?
chronic myeloid leukaemia
62
what are transposable element insertions?
virus-like sequences that copy themselves and transpose around the genome
63
what genes do autonomous transposable elements encode?
genes required for transposition such as reverse transcriptase
64
what type of transposable element are LINE elements?
autonomous
65
what do non-autonomous transposable elements use to support transposition?
transposition proteins encoded by autonomous elements
66
what type of transposable element are SINE elements?
non-autonomous
67
what is the merle phenotypes an example of?
a transposable element insertion
68
what is the function of transposable elements in the genome?
no function, they are parasitic elements
69
what is involved in cytogenetic variation?
the gain or loss of 1 or more entire chromosomes leading to aneuploidy
70
what does whole genome duplication lead to?
tetraploid cells and additional aneuploidy
71
what does whole genome duplication frequently occur in, and via what process?
cancer cells, via endoreduplication
72
how does the spindle assembly checkpoint prevent aneuploidy?
prevents progression through mitosis if chromosomes aren't correctly attached to spindle apparatus
73
how is genome variation detected?
by whole genome sequencing
74
how can copy number variants be identified by whole genome sequencing?
by identifying differences in the number of reads mapping to the reference genome
75
what are the 2 cell types the body is composed of?
germline cells and somatic cells
76
what are germline cells?
gametes (sperm and egg cells) or their precursors
77
what are somatic cells?
the cells of the body that cannot contribute to the next generation
78
what is germline variation?
genetic variation that occurs in the germline and is inherited
79
what is the germline lineage?
the lineage of cells that contributes to the production of gametes
80
what does the germline lineage begin with?
the fertilised egg
81
how many cell divisions occur before the specification of primordial germ cells?
10
82
what are primordial germ cells (PGCs)?
embryonic cells committed to the germline lineage
83
what leads to formation of a germline mosaic?
if a variant occurs in the 10 cell divisions prior to PGC specification
84
what is a germline mosaic?
when a subset of somatic and germline cells contain a variant
85
where do the primordial germ cells migrate to?
the developing gonads (testes/ovaries)
86
what happens to germ cells in the male at puberty?
cell division recommences
87
how many times per year do male spermatogonial stem cells (SSCs) divide per year in humans?
23
88
how many more divisions do committed sperm cells undergo to become mature?
4
89
what happens in the female at puberty?
menstrual cycles commence and 1 oocyte completes maturation and is ovulated each month
90
how many divisions will the germline cells of adult women have undergone?
30
91
how many divisions will the germline cells of a 30 yr old adult man have undergone, assuming he entered puberty at 15 yrs?
383
92
which is more vulnerable to acquiring variants, the male or female germline?
the male as it undergoes more division
93
how many germline SNVs are introduced via the male germline?
70-80%
94
what is the number of de novo germline SNVs dependent on?
the father's age at conception
95
what germline are most cytogenetic variants introduced via?
the female germline
96
what does the number of cytogenetic abnormalities appear to be due to?
segregation errors
97
what percentage of gametes derived from the SSC will a variant be present in if a de novo germline variant occurs in the SSC?
50%
98
how many de novo variants will each sperm have?
50-100
99
how much DNA is shared between identical twins?
100%
100
how much DNA is shared between full siblings?
50%
101
how much DNA is shared between grandparent + grandchild?
25%
102
how much DNA is shared between aunt/uncle and niece/nephew?
25%
103
how much DNA is shared between first cousins?
12.5%
104
how many positions do the genomes of 2 unrelated individuals differ at?
around 3 million
105
what are common variants shared between?
populations
106
what are rare variants unique to?
families or individuals
107
what is genetic drift?
the change in the frequency of alleles in a population due to chance
108
when is genetic drift particularly important?
when populations are small and chance fluctuations can have a large effect
109
when do genetic bottlenecks occur?
when a population is drastically reduced in size
110
when do founder effects occur?
when a small number of individuals leave a population and found a new colony
111
what has caused the high frequency of some disease alleles in breed dogs?
genetic bottleneck and then genetic drift
112
what is an example of founder effects?
the Amish population
113
what is natural selection?
a change in allele frequencies due to a change in fitness
114
what 2 types of variants can impact the cell?
coding and non-coding/copy number
115
what do coding variants lead to?
a change in the amino acid composition of the protein product
116
what do non-coding variants/copy number variants lead to?
changes in the amount of protein product produced
117
what variant types can coding variants cause?
missense, nonsense, in-frame insertion or deletion, frameshift, splicing, gene truncation via rearrangement, fusion gene
118
what happens in a missense variant?
causes a single amino acid to be switched from 1 to another via an SNV variant
119
what happens in a nonsense variant?
causes the introduction of a premature stop codon via an SNV variant
120
what happens in an in-frame insertion or deletion?
indel variant of 3bp or multiple of 3bp causes insertion or deletion of 1 or more amino acids
121
what happens in a frameshift variant?
indel or other type of insertion/deletion variant inserts or deletes a number of bases that isn't a multiple of 3 - changes reading frame, leads to premature termination of protein
122
what happens in a splicing variant?
causes a change to splice donor or splice acceptor site which causes abnormal splicing such as exon skipping
123
what happens in a gene truncation variant via rearrangement?
structural variant leads to gene truncation
124
what happens in a fusion gene variant?
structural variant brings 2 genes together, they splice together to forma a novel in-frame fusion gene
125
what are examples of non-coding variants?
variants in promoters, enhancers, 5' or 3' UTRs, non-coding RNAs such as miRNAs, copy number variants, cytogenetic variants
126
what do dominantly acting variants do?
generate a phenotype when present in at least 1 copy in the cell regardless of the number of additional chromosomal copies
127
what do recessive variants do?
generate a phenotype only when the variant is carried by all chromosomal copies present within the cell
128
what is co-dominance?
where the impact of both alleles is visible in the heterozygous phenotype
129
what is positive selection?
selection acting on a phenotype to increase allele frequency in a population
130
what types of fitness advantage are there?
adaptive, selfish, artificial
131
what is an adaptive fitness advantage?
one that enhances individual's adaptation to environment
132
what is a selfish fitness advantage?
one at the level of the cell rather than the level of the individual
133
what is artificial fitness advantage?
one caused by human intervention (like dog breeding)
134
what does negative selection do?
acts on a phenotype to reduce allele frequencies in populations
135
what is balancing selection?
an interaction between positive and negative selection which acts to maintain several alleles in population
135
what can most diseases be broadly categorised into?
single mutation, complex genetic, infectious, cancer
136
what are single mutation diseases?
diseases that arise due to a single mutation
137
what are complex genetic diseases?
diseases that don't have a single genetic cause
138
what do infectious diseases develop due to?
exposure to an infectious agent
139
what does compound heterozygosity involve?
2 mutations in the same gene
140
what are de novo mutation diseases?
diseases that occur due to inheritance of a newly-arising germline variant
141
what are de novo mutation diseases that are passed on to offspring known as?
autosomal dominant/sex-linked/mitochondrial inherited diseases
142
what are many miscarriages likely due to?
de novo mutations that are incompatible with embryonic development
143
when do autosomal dominant diseases with severe phenotypes in humans tend to onset?
in adulthood as otherwise wouldn't be inherited
144
what are examples of autosomal dominant diseases in humans?
Huntington's disease and polycystic kidney disease
145
what are compound heterozygotes of autosomal recessive inherited diseases?
affected individuals that inherit 2 different faulty copies of the same gene (each carries distinct disease allele at different locus)
146
what are recessive lethal alleles?
alleles that are incompatible with fetal development in the homozygous state
147
which individuals are at a significantly higher risk of autosomal recessive disease?
those with a family history of consanguinity
148
what is reduced penetrance?
when different individuals harbour the same disease genotype and only some individuals develop the disease
149
what can cause reduced penetrance?
accumulation of somatic mutations, mosaicism, variable copy number of disease haplotype, epigenetic and environmental factors
150
what is variable disease severity/expressivity?
when individuals with the same disease develop less severe symptoms
151
what is an example of variable disease severity in dogs?
double merle phenotype
152
what causes the double merle phenotype of dogs?
inheriting 2 copies of a SINE element insertion in the SILV gene
153
what does gene therapy involve?
delivery of normal copies of genes directly to target cells in individuals affected with genetic diseases
154
what are the gene copies normally packaged into in gene therapy?
non-integrating viruses
155
what is mosaicism used to refer to in the context of disease?
the situation when a de novo disease mutation arises during embryonic development
156
what is a germline mosaic individual?
when a de novo mutation disease is present in a subset of germline cells and a subset of somatic cells
157
what does transmission frequency depend on in germline mosaic individuals?
the proportion of germline cells which carry the mutation
158
what is a clone?
a set of cells with a common origin (common ancestor)
159
somatic evolution of cancer?
occurs when a somatic cell of the body acquires a set of somatic mutations that cause that cell to acquire a selective advantage relative to other somatic cells
160
what sort of evolution is cancer an example of?
selfish evolution
161
what is the role of somatic cells from an evolutionary perspective?
to nourish and optimise the germline in order to maximise genetic contribution to the next generation
162
why is the evolution of cancer usually self-destructive?
the continued growth and survival of the cancer is not compatible with continued survival of the host upon which the cancer relies for nutrients and support
163
what are neoplasms?
all abnormal clonal cell growths in the body
164
when are neoplasms known as benign tumours?
if they remain localised, respect tissue boundaries and don't have potential to invade host tissues
165
when does a neoplasm become malignant tumours?
when it disrupts tissue boundaries and invades host tissues or has the potential to
166
what is cancer?
a malignant clone of cells which arises when a somatic cell follows a programme of selfish positive selection maximising the fitness of the cell instead of the cell body
167
how many somatic mutations do somatic cells get per cell division?
2-10
168
what are neutral somatic mutations known as?
passenger mutations
169
what are passenger mutations?
somatic mutations with no effect on the cell
170
what are driver mutations?
somatic mutations that confer the cell with phenotypes that confer a selective advantage in terms of proliferation and survival
171
what phenotypes do selfish positive selection act on?
phenotypes that confer a growth or survival advantage to the cell
172
how are somatic mutations in cancers discovered?
by whole genome sequencing- any genetic variant not found in normal DNA is considered somatic mutation
173
how many somatic mutations do most human cancers have?
between 1000 and 30000
174
how are driver mutations in cancers discovered?
by searching for the same mutation occurring in independent cancers from different patients
175
what is the most common driver mutation in BRAF V600E?
an SNV which causes a missense mutation
176
how many driver mutations do most cancers have?
between 1 and 10
177
how many cancer genes are known in humans?
743
178
what is a cancer gene?
a gene known to harbour driver mutations in human cancer
179
what are oncogenes?
dominantly acting cancer genes where mutation of 1 copy is sufficient to trigger the selective advantage
180
what are 2 examples of oncogenes?
KRAS and BRAF
181
what is BCR-ABL1?
a dominantly-acting fusion gene created by the Philadelphia chromosome mutation
182
what mutation creates BCR-ABL1?
Philadelphia chromosome mutation
183
what is MYC?
a dominantly acting cancer gene
184
what are double minutes?
tiny circular DNA elements created by unbalanced structural variants
185
what can double minutes lead to?
massive copy number amplifications
186
what are tumour-suppressor genes?
recessively-acting cancer genes where both copies must be lost in order for selective advantage to be gained
187
what are 2 examples of tumour-suppressor genes?
CDKN2A and PTEN
188
what is CDKN2A also known as?
p16/ARRF
189
what is TP53?
a (usually) recessively acting cancer gene
190
what is PTEN?
a recessively acting cancer gene
191
what cancers are the most common in humans?
carcinomas
192
what cancers are relatively common in dogs and rare in humans?
sarcomas
193
what cells are carcinomas derived from?
epithelial
194
what tissues are sarcomas derived from?
connective tissue
195
how can cancer therapies lead to therapy resistant cancers?
therapy imposes a selective pressure on cancers- if resistance mutations are present these will be strongly positively selected
196
what is an example of a therapy resistance mechanism in ovarian cancer?
the reversion of BRAC1/2 mutations to wild-type in PARP inhibitor resistant ovarian cancer
197
what are transmissible cancers?
cancers that survive beyond the deaths of their original hosts by transmission of living cancer cells between hosts
198
how many known transmissible cancers are there?
14
199
what is chimerism?
the presence of cells derived from 2 different individuals (2 separated fertilised eggs) in the same body
200
what is a tetragametic chimera?
when fraternal twin embryos fuse in utero forming a single embryo
201
what are blood chimeras?
a pair of fraternal twins who exchange blood cells in utero
202
what % of fraternal twins have blood chimerism?
10%
203
which sex chromosome is smaller?
Y
204
what are the regions at the tips of the Y chromosome that are homologous with the X chromosomes?
the pseudoautosomal regions (PAR)
205
what allow the X and Y chromosomes to pair and recombine during meiosis in the male?
the PARs on the tips of the Y
206
what are many of the genes on the Y chromosome involved in?
spermatogenesis
207
what is the distal half of the long arm on the Y chromosome like?
made up of highly repetitive DNA and is heterochromatic
208
what is the region of the Y chromosome involved in sex determination?
the SRY gene
209
what does the SRY gene encode?
a transcription factor that activates a testis-forming pathway early in development
210
what is the embryonic gonad described as before the SRY pathway is triggered?
indifferent- meaning it is capable of developing into either a testis or ovary
211
what is dosage compensation between the mammalian sexes achieved by?
inactivating one of the 2 X chromosomes in females
212
how many X linked recessive traits are known in humans to date?
515
213
what % of daughters of females affected with an X-linked dominant disorder will be affected?
50%
214
what is the important difference between the pedigree of an X-linked dominant trait and an autosomal dominant condition?
lack of father to son transmission for X linked dominant trait
215
is X inactivation always the maternal chromosome?
no, random which is inactivated
216
which specific genes are included in the genes that escape X inactivation?
the PAR genes
217
what gene does X inactivation require the expression of?
the non-coding RNA gene Xist
218
what does Xist expression initiate?
a hierarchy of epigenetic events that lead to progressively stronger silencing of the inactive X
219
what are the repressive histone modifications found along the length of the inactive X?
H3K27me3 and H3K9me3
220
what are epigenetic modifications?
chemical marks on DNA and post-translational modifications to chromatin-associated histone proteins
221
what dinucleotides does DNA methylation occur on in mammalian cells
CG dinucleotides
222
why is DNA methylation symmetrical on the 2 DNA strands in mammals?
it occurs on CG dinucleotides
223
what maintains DNA methylation during DNA replication?
the maintenance methyltransferase Dnmt I
224
how is DNA methylation acquired anew?
by de novo DNA methyltransferases
225
what does deamination of unmethylated cytosine convert it to?
uracil
226
what does the cytosine->urine conversion cause cell to do?
recognition as alien in DNA, repair back to cytosine by cell
227
what is produced when 5'-methylcytosine is deaminated?
thymine
228
what happens if the methylcytosine -> thymine shift is not corrected?
the change becomes a permanent mutation of C to T, CPG dinucleotide lost
229
what % of CpG dints are methylated in somatic cells of mammalian genomes?
75%
230
what % of their expected frequency do CpG dints occur at?
21%
231
what is the exception to CpG depletion in mammals?
CpG islands which are generally hypomethylated so have retained CpG content
232
what does loss of the heterochromatic marks H3K9me3 and H3K9me2 result in?
inability of chromosomes to segregate properly
233
what are the 3 essential processes in cells that epigenetic modifications regulate?
chromosome architecture, silencing of repetitive transposable elements, somatically heritable changes in gene expression
234
what is an example of 2 epigenetic modifications that are incompatible with the presence of each other?
H3K27me3 and H3K27Ac
235
what is an example of 2 epigenetic modifications that go hand in hand?
DNA methylation and H3K9me3
236
what suggests that DNA methylation can sometimes be a consequence of gene repression not a cause?
sometimes acquired at repressed promotors long after gene has been repressed
237
is epigenetic information generally inherited from 1 generation to the next?
no
238
when is DNA methylation erased from the germline?
epigenetic marks are erased early in PGC development
239
what does PGC stand for?
primordial germ cell
240
when does establishment of new epigenetic marks occur in the male germline?
on prospermatogonia during foetal development
241
when does establishment of new epigenetic marks occur in the female germline?
after birth during the growing oocyte phase
242
when does the second phase of genome-wide epigenetic erasure and re-establishment occur?
immediately after fertilisation
243
what mechanisms remove epigenetic marks immediately after fertilisation?
active (enzymatic) and passive (dilution during DNA replication)
244
what are genomic imprints?
DNA methylation marks that are established in different places in the male and female germlines and are resistant to the 2nd wave of epigenetic reprogramming immediately after fertilisation
245
how many genes have been identified that are expressed solely from 1 of the 2 parental chromosome homologues?
around 200
246
which allele expresses and represses the IGF2 gene in developing embryos?
the paternally inherited chromosome homologue expresses, the maternally inherited one represses
247
what regulates the monoallelic expression of an imprinted gene?
DNA methylation that differs on the 2 parental chromosomes
248
what is the imprinting control region?
a differentially methylated region (DMR) located at the promoter of an imprinted transcript or in the vicinity of an imprinted locus
249
when are ICRs established?
in the germline
250
how are imprinted genes often arranged?
in clusters, with a single ICR regulating the monoallelic expression of all imprinted genes in the cluster
251
what do imprinting disorders in humans arise from?
mis-expression of imprinted genes
252
what can cause imprinting disorders in humans?
uniparental disomy, or epimutation
253
what does epimutation cause in the ICR?
it to lose its appropriate differential methylation status and hence normal imprinting perturbed
254
why is evidence as to whether the environment talks to the genome (via epigenome) hard to ascertain?
1. it's hard to rule out genetic effects 2. it's hard to determine whether an observed epigenetic change associated with an environmental influence is causal or a secondary consequence of the phenotype
255
what does undernourishment of the embryo in utero lead to in mice?
developmental delay, smaller pups and adult onset diseases, effects also seen in F2 generation
256
what is the Dutch Hunger winter an example of?
how in utero nutritional compromise during a defined developmental window can lead to adult onset disease in offspring
257
how long is the mitochondrial genome?
16.5kb
258
characteristics of the mitochondrial genome?
16.5kb long, circular, each mitochondrion has several copies (2-10), 27 genes, no introns
259
how many genes does the mitochondrial genome contain?
27
260
how much of the mitochondrial genome makes a functional gene product?
all but 1kb of it
261
what does the mtDNA encode?
some of the components needed for mitochondrial protein synthesis on mitochondrial ribosomes
262
what does the endosymbiont theory propose?
the 2 genomes (mitochondrial and nuclear) originated when a type of aerobic prokaryotic cell was endocytosed by an anaerobic eukaryotic precursor
263
how are mitochondria inherited?
matrilineally
264
why do sperm mitochondria not contribute any mtDNA to the embryo?
they are degraded upon fertilisation
265
what is homoplasmy (mtDNA)?
every mtDNA is the same
266
what is heteroplasmy (mtDNA)?
can be a mixed population of normal and mutant mtDNAs
267
what is the threshold level for most pathogenic mtDNA mutations?
60-80%
268
why can level of heteroplasmy change over time?
due to the random way mtDNAs are replicated and segregated
269
characteristics of mtDNA replication?
stochastic (random), not directly linked to cell cycle
270
how many mitochondria do egg cells contain?
more than 100000
271
where do mitochondrial disorders show the greatest impact?
in tissues of high energy requirements- muscle and brain
272
when did the UK government make mitochondrial therapy legal?
Feb 2015
273
what is MRT?
mitochondrial replacement therapy
274
when is the nuclear genome transferred in metaphase II spindle transfer MRT?
before fertilisation of the egg
275
when is the nuclear genome transferred in pronuclear transfer MRT?
after fertilisation of the egg
276
what does MRT require?
preimplantation genetic diagnosis and in vitro fertilisation
277
what is a polymorphism?
an allele with a frequency <1%
278
what is a haplotype?
a group of alleles inherited from a single parent on the same chromosome homologue
279
what does the Hardy-Weinberg law provide?
a mathematical relationship between allele and genotype frequencies
280
what is the hardy weinberg law?
p + q = 1, p2 + 2pq + q2= 1
281
what are the requirements for the hardy-weinberg law to be applicable
no mutation, random mating, no gene flow, infinite population size, no selection
282
example of an allele that doesn't obey Hardy-Weinberg predictions?
sickle cell anaemia allele HbS provides comparative resisitance to malaria
283
which genome variants are more likely to be neutral, those in introns or exons?
introns
284
what do genetic linkage studies do?
follow the inheritance of a trait in an affected family (pedigree) and look for co-segregation of the phenotype with alleles of polymorphic genetic loci from across the genome
285
what are identical twins?
monozygotic
286
what are non-identical twins?
dizygotic
287
what are concordant twins?
twins that both show a trait
288
when are twins discordant?
if only 1 shows a trait
289
for which is the concordance rate higher, monozygotic or dizygotic twins?
monozygotic twins
290
what does the concordance rate in monozygotic twins range from?
6-100%
291
how can twin studies be used to obtain an idea of the contribution of genetics to a disease?
comparing ratio of concordance between monozygotic and dizygotic twins
292
what is a GWAS?
a genome wide association study
293
what is a genome wide association study?
the approach of scanning the genome for regions contributing to complex phenotypes
294
what happens in a GWAS screen?
a large number of individuals with the trait/disorder of interest are genotyped alongside a large set of neutral control individuals from the same population
295
how is GWAS data presented?
in the form of Manhattan plots where the x axis shows the chromosomal location of each SNP, each dot represents an SNP, y axis shows statistical significance of association of each SNP with the particular trait
296
what is the OMIM database?
online mendelian inheritance in man database, has info on all known monogenic disorders on over 15000 genes
