MCO Flashcards
1
Q
reasons to understand genetics
UNDERSTANDING FUNCTION
A
we experiment to find the allele
2
Q
Genomics
A
technology for sequecing
TECHNOLOGY used to generate LARGE DATASETS of digital information
3
Q
Genetics
A
Method of experimentation (the methodology)
used to understand the cause and effect between genes and phenotypic variation
4
Q
the centers goal
A
o apply genetic information to develop therapies and clinical risk assessment tools for diseases in individuals and the general population.
5
Q
model organisms
A
are how we know about genome
6
Q
Holobiont
A
Host (multicellular) + microbiome (beneficial)
7
Q
viable systems model
A
urban eaters/eden/ eat
8
Q
african globe lily
A
-has microtubules
-huge thicker chromosomes when condensed during mitosis
-thicker than the longest human chromosome
9
Q
a human cell contains over
A
two metres of DNA
10
Q
chromosome structure
A
telomeres
centromeres
euchromatin and heterochromatin
11
Q
telomeres
A
-ends maintain length
-repeat structure
12
Q
centromere
A
-spindle attachment
-satellite DNA
13
Q
euchromatin and heterochromatin
A
packaging of DNA, RNA and protein
14
Q
chromosomes - p
A
short arm
15
Q
chromosomes - q
A
long arm
16
Q
chromosome structure and staining
A
pink = nucleic acid banding patterns provides address because two pairs that look different with different number of bands
=small deletion of some infs
mapping related to trait
17
Q
drosophila
A
polytene chromosomes from salivary glands
these arise because replicated DNA strands do not separate during interphase
visible bands provide high resolution physical Map position
18
Q
the era of genome sequence
A
chromosome and position
physical size (base pairs)
gene names and position
19
Q
genotype =
A
aligning chromosome pairs copying them
20
Q
interphase
A
chromosomes and organelles replicate
21
Q
prophase
A
nuclear membrane breaks down
spindle begins extending from poles and attaches to centromeres (kinetochore)
22
Q
in mitosis it is _______ attachment
A
bipolar
23
Q
in anaphase sister chromatids are now
A
chromosomes
24
Q
cytokinesis
A
CHROMSOMES DECONDENSE
cells divide
25
cohesin
protein that provides attachment for sister chromatids
26
kinetochore
attaches to chromatids and spindle fibres
27
seperase
enzyme that breaks down cohesion
28
all cells are same ploidy
same number of chromosomes
29
prophase 1
-centrosome splits and move to poles
-DNA condensing
-homologous chromosomes align and synaptonemal complex forms
-double strand breaks arise and chiasmata form
-nuclear membrane breaks down
-spindle begins to form
-DNA fully condensed , synaptonemal complex breakdowns and monocular kinetochores attach chromosomes to spindle
30
metaphase 1
kinetochores have aligned at the equator (metaphase plate)
31
anaphase 1
monopoly attachment pulls homologous chromosomes to opposite poles
32
telophase 1 and cell division
haploid cells have formed
-shuffling the deck has occurred through independent assortment and crossing over
33
meiosis results in
four genetically distinct haploid cells
34
prophase stage 1- leptotene (thin thread stage)
-chromosomes start to condense and become visible
-homolog pairing begins
-double-stranded DNA breaks are introduced (potential sites for crossing over)
35
prophase stage 2-zygotene (paired threads stage)
-a synaptonemal complex begins to form between homologous pairs (synapsis)
-paired homologs now referred to as bivalents
36
prophase stage 3-pachytene (thick thread stage)
-condensing of chromosomes continues
-synaptonemal complex is complete
-bivalents now have four sister chromatids (tetrads)
-crossing over is completed
37
prophase stage 4- Diplotene (two thread)
-synaptonemal complex dissembles
-each pair of sister chromatids begins to separate
-chiasmata = visible regions of cross-over between non-sister chromatids
38
prophase stage 5-Diakinesis (moving apart stage)
-chromsomes repel each other
-non-siter chromatids remain loosely associated via chiasmata
-nuclear membrane and nucleolus disappear
-monopolar attachment of chromosomes to spindle fibres
39
synaptonemal complex
function: facilitates late stages of recombination
prevents different homolog pairs from getting entangled
40
meiosis 1 maintain
policy level for sexual reproduction
41
genetic shuffling
occurs in meiosis 1 by independent assortment of homologous chromsomse and by cross over of chromosome arms between sister chromatids
42
studying genetics look at
variation in progeny
43
biochemistry studying genetics
study proteins in test tube
44
molecular biology upstanding genetics
DNA/RNA in a test tube
45
Eric lander
mission of improving medicine with genome-based evidence
46
Gregor mendel author of
experiments in plant hybridisation in 1865
47
experimental method genetics to reveal cause and effect
1)assemble robust experimental system
2)design and perform first experiment and generate lots of quantitative data
3)repeat same experiment with different starting material
4)analyse the collective data and derive a predictive model
5)devise and execute experiment to test predictions
48
F1 =
first generation PRODUCED
49
first law of inheritance
heredity is controlled by paired factors or alleles of genes
50
Bateson (1861-1926)
coined terms genetics and epistasis
-looked at different organisms and conducted controlled crosses looked at progeny
51
Roland biffen 1879-1949
resistance to yellow rust wheat plants was identified as a ingle mendelian trait
-FIRST DEMONSTRATION OF APPLIED GENETICS
52
phenotypic dominance and first law of inheritance demonstrated the importance of
experimental model organisms
53
experimental genetic models are how we understand
immunity (plant and animal)
54
Discrete traits
-complete full dominance
-environmentally stable phenotypes
55
artificial mutation
main source of genetic variation used for research in experimental genetic models
56
natural variation
the main resource for translational genetics
57
discrete traits are unusual
in a species
58
complete dominance
maximum expression
AA
59
incomplete dominance
maximum + intermediate
AAAa
60
overdominace
intermediate Maximum
61
penetrance
the extent to which a particular gene or set of genes is expressed in the phenotypes of individuals carrying it, measured by the proportion of carriers showing the characteristic phenotype.
62
genetype x environment [rimoridial dwarfism
primordial = genetic cause as it is a gene mutation
hypopituitary dwarfism is mutation but can be treated with growth hormone therapy
63
gibberrellic acid (GA)
like human growth hormone for plants
some dwarf mutants in plants are GA-responsive
other dwarf mutants are not GA-responsive
64
redundancy
duplicate genes that provide the same function
65
complementary genes
the phenotype depends on both genes being functional
(e.g., different steps in same biochemical pathway)
66
polygenic variation
1918 fisher developed mathematical approach to explain mendelian factors as the basis of quantitative (polygenic) traits
1920 drosophila (truncate wings) shown to arise from mutations in multiple unlinked factors
67
Ronald A fisher (1890-1962)
found number of F2 in each genotype was distributed normally
68
Genetic mapping of complex traits
objective
to localize (map) genes that underlie a phenotype on the basis of correlation with DNA sequence variation.
69
Genetic mapping of complex traits
Methods
* Linkage mapping population: progeny derived from a controlled cross of known parents (chosen because they exhibit contrasting phenotypes and are polymorphic in many genome-wide DNA markers
70
mapping populations pros and cons
Pros:
1)No question of dominance
2)Immortal lines
3)Powerful data accumulation
4)Reproducibility
5)GxE experiments possible
6)Inter-mating inbreds, to test
genetic models
cons = finite resources
71
LOD score: a statistical test for linkage
logarithm of the odds
= Log10 (likelihood that two loci are linked)/(likelihood that two loci are unlinked)
72
simple medelian (tractable-easy to investigate)
-single gene mutation associated with disease
-disease is due to a typically rare allele in the population (1 in >2000 individuals)
-readily defined pattern of inheritance
73
complex or multifactorial (difficult to investigate
-alleic variation in multiple genes associated with disease
-cumulative affect of weakly expressed common alleles
-disease risk is typically influenced by non-genetic factors
74
What is pedigree analysis?
-use of diagram to summarise the inheritance of discrete trait (phenotype) in a family history
75
coloured in square on pedigree charts
usually has phenotype of interest
76
diamond shape on pedigree charts
unknown sex
77
half coloured shape on pedigree charts
heterozygote
78
why do pedigree analysis?
Knowledge about simple ‘Mendelian’ traits
ethical limits (controlled matings are not possible)
limits
-small sampes
-inaccurate or incomplete data
79
aims of pedigree analysis
Determine the mode of inheritance
Sex-linked or autosomal
Dominant or recessive
Calculate the probability of an affected individual based on recent family history
(e.g., for genetic counseling)
80
Autosomal recessive inheritance
dd = disease
81
Autosomal dominant inheritance
DD can be lethal so all heterozygotes will be Dd
82
If two affected parents have unaffected children, then recessiveness can be ruled out
True for both autosomal and sex-linked traits
83
If unaffected parents have an affected child,
then dominance can be ruled out
true for both autosomal and sex-liked traits
84
If unaffected parents have an affected daughter,
then
dominate and x-linked recessive disorder can be ruled out
85
types of molecular markers
SSR
Simple Sequence Repeats
micro satellites (2-4 base pair repeats)
minisatlleties (variable number tandem repeats)
86
Types of molecular markers SNP
Single Nucleotide Polymorphisms
87
Sir
more and fewer sequence repeats
more = bigger PCR product
Fewer = Smaller PCR product
88
linkage mapping with SSrs
1)collect pedigree information
2)ue PCR and blood samples from living family members use gene electrophoresis
3)statistical linkage
4)identify new molecular markers from within the locus
89
Barbara McClinktock 1983 Nobel prize for
discovering transposable elements
-looked at maize in two different places
-then found mutations can be turned on or off
90
Transposable element
DNA sequence that can change position within its genome
91
umping occurs during mitosis and is affected by
the environment
92
transposable elements can enter
promotors =switching gene on or off
exons = non-functional
Not in gene = no effect
93
Jumping genes effect ..
generate transposable elements in plants and animals
94
epigenetics
heritable changes in gene expression not caused by changes in DNA sequence
methylation = methyl group an epigenetic factor can tag or repress genes
95
Ruth Sager =
discovered DNA in mitochondria and early pioneer in cancer genetics
INHERITANCE VIA CYTOPLASM TYPICALLY FROM MOTHER ONLY
96
biochemical evidence of symbiosis
mitochondria communicate with the nucleus via trafficking of proteins and RNAs
97
genetic evidence of symbiosis
the nucleus contains genes that encode mitochondrial proteins
98
mitochondrial genome
circular genome
contains genes for tRNAs, r RNAs, cytochrome oxidase ...
humans small genome as 16 kb
99
chloroplast genome
contains genes for redox proteins involved in electron transport for photosynthesis
also contain lots of introns
100
extranuclear inheritance
does not involve meiotic segregation
organelles are acquired at cell division from teh maternal cyctoplasm
GENOTYPE AND PHENOTYPES OF OFFSPRING IS THE SAME AS THE MOTHER
101
chloroplast inheritance and who found that
maternal inheritance following mitosis
CORREN who found that by observing chloroplasts and leucoplasts (no chlorophyll production)
no contribution from pollen
102
yeast mitochondrial inheritance *IMPORTANT
most yeast is haploid
normal vs petite
genetic evidence from two types of mutants
segregational mutants = mendelian segregation following meiosis and genes are located in the nucleus PREDICTABLE RATIO
vegatative mutants = non-mendelian pattern of inheritance and genes are located in teh mitochondria
103
segregational petites
two haploid cells create zygote then meiosis resulting in a tetrad of progeny each
resulting tetrad shows a 2 : 2 ratio of wild type to petite this result indicates mendelian inheritance in yeast
104
vegetative petites (non mendielian)
neutral or suppressive
each tetrad produces a 4:0 ratio of allwild type to petite
all petites produce a 0:4 ratio of wild type to petite
105
yeast petite mutants
neutral petites lack most of their mitochondria DNA
-suppressive petites lack only small segment of mtDNA
-yeast offspring inherit mitochondria from both parents
106
why petite colonies
suppressive petite mitochondria replicate faster and dominate
107
heteroplasmy
occurrence of both forms of mitochondria in teh same cell results in variable levels of expressivity
108
maternity analysis phylogenetic systematics ad population genetics WHY
-easy to isolate and PCR amplify mtDNA due to high copy number per cell
-maternal inheritance mtDNA enables analysis of maternal population structure without confusion of male-mediated gene flow
-no recombination of mtDNA so very slow to evolve
-mutations that do occur are rapidly fixed in a population
109
maternal inheritance
for example shells in snails maternal factors(protein or mRNA) that are deposited in the oocyte prior to fertilisation these are typically important for development
110
genomic imprinting
A form of gene expression in which an allele of the affected gene is marked imprinted in one of the parents and can be passed on through meiosis to the offspring
111
chromosomal mutation
-changes in the chromosome number per cell
-large-scale (segmental) change in chromosome structure
-VISIBLE BY MICROSCOPE
112
why investigate chromosomal mutations?
-cytological insight into meiosis
-medical insight in causes of genetic disease
-molecular insight of how genes interact through a genome
-evolutionary insight
113
terms indicating number of chromosomes
-monoploid - n
-diploid - 2n
-triploid - 3n
-tetraploid- 4n
114
Aneuploid
change in number of some but not all chromosomes
115
monoploidy
-non viable in most animal species
-deleterious mutations would be effective (as any mutation is expressed)
exception: social insects males are monoploid and develop by PARTHENOGENESIS (gametes from mitosis)
116
paleotetraploid
functionally diploid but 1000s of years ago were tetra but over time genomes seperated
117
polyploidy and size
size increases with higher policy (not number of)
118
two origins of polyploidy
autoplyploid = derived from teh SAME diploid species
Allopolyploid = different progenitor species
119
organ of hexaploid wheat
-42 chromosomes
-derived from three ancestral diploid species
120
chemically induced polyploidy is done by
colchicine which can be used to disrupt spindle assembly and thereby block chromosomal segregation
121
meiosis in a triploid
produces aneuploid gametes consequence = highly sterile
122
what causes change in chromosome number?
non-disjunction = when meiosis malfunctions
triatomic possibly lethal
monosomic = lethal
123
miss-aligned repeat sequences
consequence = unequal crossing over
gain or loss of repeats
124
pericentric inversion
encompasses teh centromere
125
aracentric invesion
does not encompass the centromere
126
invasion heterozygote
twisting of chromosomes large segments creates inversion loop visible in meiosis
127
large segmental inversions
if no recombination within an inversion loop
then no deletion of duplication possible
128
a crossover within an inversion loop creates
dicentric and eccentric chromosomes
129
reciprocal translocation
heterozygous translocation one pair interchanges and one pair normal
homozygous translocation = both pairs interchanged
130
cancer by somatic translocation
ABL encodes a protein kinase that transduce a signal for cell proliferation which is inherited by a growth factor
chimeric protein is always active therefore cancerous
131
population
a group of individuals of the same species that are able to interbreed
some species occupy a wide geographic range and are divided into sub-populations
132
purpose of population genetics
-genetic structure of a population
(number of alleles within a gene pool)
-geographic patterns in a distribution of allelic variation within and amongst sub-populations
-temporal changes in genetic structure of a ppulations
133
application of population genetics
-species conservation and utilisation of biodiversity
-essential for Genome-Wide association mapping (GWAM)
134
genetic structure
-genotype frequencies
number of characteristic / total in population
135
genetic structure allele frequecies
-total number of a specific gene (r) / number of alleles
136
hardy Weinberg principle
method for investigating the movement of alleles in a population
essential for understanding the mechanisms isms of evolutionary change
assumes several starting parameters
-infenetly large population
-random mating amongst infdividuals
-no new mutations, migration or natural selction
137
hardy Weinberg principle
look up on good notes on computer
138
change in genetic structure
Mutation
-creates new alleles
-ultimate source of genetic variation
139
change in genetic structure
migration
-new individuals move into teh population
-introduces new alleles (gene flow)
140
change in genetic structure natural slection
-some genotype produce more offspring
-differences in survival or reproduction
-leads to adaptatio
141
directional selection
-favours individuals at one extreme of a phenotypic distribution which have a greater reproductive success in a particular environment
142
stabilising selection
-favours survival of individuals with intermediate phenotypes
-extreme phenotypes are selected against
143
initiator
introduction of new favoured allele
144
disruptive selection
-favours the survival of two or more different genotypes that each produce different phenotypes
-likely to occur in populations that occupy diverse environments
-members of the populations can freely interbreed
145
balancing selection
two or more alleles are kept in balance therefore maintained over genertions
heterozygote advantage
146
change in genetic structure
genetic drift
-random loss of alleles from a population due to a chance event
-large populations are more stable than small populations
-result in loss of genetic variation
147
genetic drift is a
random event does not select for a phenotype
148
genetic bottlenecks
-sudden decrease in population size caused by adverse environmental factors
-serious concern for endangered species
-the black plague eliminated 75% of some European populations during the mid 1300s
149
founder effect
dispersal and migration that establish new populations with low genetic diversity
150
non random mating
assortative mating
-individuals with similar phenotypes are more likely to mate
-increases frequency of homozygotes
151
non-random mating
disassortative mating
-dissimilar phenotypes mate preferentially
-favors heterozygosity
152
Dawn of the hominins
-found in the sahal area shows that the earliest hominids were wide ranging across Africa (eastern and southern)
153
hominids =
great apes + gibbons
after the split with pan
154
early hominid sites
-austrolopith sites of eastern and southern africa
-A ramidus and Ar kadabba in middle awash possibly stem group from which all hominids evolved
-first australopithecine was found by Raymond dart
155
The taung child
-originally rejected as ancestor of humans because of LOW brain capacity
156
the laetoli footprints
-3.6 MYA definitive evidence of bipedalism
157
Lucy
-small brain
-highly sexually dimorphic species
-climber and walker
158
Pelvic evolution for bipedalism - a bucket for your guts
-pelvis is Lucy has turned round to form a shallow support of the viscera of the body
-legs are still quite lateral (waddle going on)
159
Obstetrical consequences of bipedalism LUCY
-would have been able to give birth to a baby with brain weight limited to 140-160 g
160
less developed birth linked to changes in life history
-by observing dental development differences between humans and chimps
-less developed infants means more care required longer development phase
161
Why stand up?
Arboreal bipedalism gaining favour
-prevents ranging on ground(dragging knuckles)
162
features of robust morphology Hominds
Australopithecine trend towards heavier grinding with stronger muscle attachments and a flattening and deepening of the face
163
`hominis evolved during a changing climate
-robusts seems to have been better adapted to the savannah environment the more gracile environment
-robustus persisted while the genus homo evolved from either Africans or ferns lineages
164
many hominis?
-much debate still about whether various lineages should be grouped together and just represented wide range of phenotypes
165
broad trend to increasing brain capacity
-increased brain size for given body weight over time
166
cultural evolution :stone traditions
-oldowan started with australopithecians 2.5 MYA
-acheullian industry more complex is associated with homo Erectus beginning 1.7 MYA
167
Homo habilis- one or two species
-many think morphological distance between Australopithecus and homo Erectus is too narrow another species
some say dimorphism is observed may actually be two species
168
why did the brain enlarge?
beneficial for
male hunting
expensive tissue hypothesis = posits that in order for brains to grow
scavenging = what h. Habilis was capable of
-plant use = hunting is ecologically risky
169
Java man the first missing link
-Haeckel coined the term pithecanthropus (ape man) from Darwins prediction of a missing link
-dubois found this missing link in java in 1984 rejected as it was insisted it was a gibbon
170
H erectus expansion into SE asia
-Dtaes now suggest that H erectus reached java as much as 1.7 MYA meaning very early dispersal out of africa
171
The enigma of flores
-flores has H erectus bu 800 Kya which would have required seafaring which is incredible in itself
172
More SE asian hoinins
-homo luzonensis 67,000 years oldest homo in philipines
-tooth morphometrics place it as direct from archaic humans
173
Divergence of African and asian H erectus
-oldest African H erectus dates from 1.89-1.95 MYA from e Africa older than Asian
174
Asian H erectus lacked acheulian industry
-archeulian industry begins 1.5 MYA with h erectus in Africa
-asian does not have this which suggests it left before (fits with JAVA dates)
-means they left africa early
175
Turkana boy
-most complete H erectus skeleton (1.65 MYA) would-be 6 foot
-had modern body proportions
176
Locomotor evolution
-tall sim proportions there by 1.8 MYA in H erectus long legs for running
-SA:V allow loss of heat
177
Archaic humans
hard to define groups between erectus and neandrathals
178
Oldest homo sapians
-morphometric analysis shows it be like recent modern humans (RMH) but still evolving
179
Oldest European H sapiens
modern h sapiens mixture of neandrathals an modern human features.
180
Upper paleolithic revolution
-industries changed dramatically to become more aggressive use of handles and blades
-that quickly over ran the known world occurred 50,000 years ago
181
did the anatomically modern human from Africa replace all regional archaic forms?
washer genetic input from regional archaic forms
