Genetics: Genome, Chromosomes, Pedigrees, Abnormalities Flashcards
1
Q
How many chromosomes do humans have?
A
22 pairs of autosomes, 2 sex chromosomes (XX or XY)
2
Q
(T/F) Chromosome number is the same between all mammals
A
False
3
Q
Genotype
A
Genetic composition of an individual; alleles at a specific genetic locus
4
Q
Phenotype
A
Observable expression of a particular gene(s)
5
Q
Penetrance
A
Frequency with which a genotype manifests itself in a given phenotype
6
Q
Relationship of genotype, phenotype, and penetrance
A
Phenotype is the result of a combination of penetrance and genotype
7
Q
Chromosomes are condensed in…
A
Metaphase
8
Q
Metacentric
A
Centromere in middle of chromosome
9
Q
Acrocentric
A
Only a small amount of repetitive DNA above centromere
10
Q
Submetacentric
A
Short p arms above centromere
11
Q
Karyotype
A
Number and appearance of complete set of chromosomes in nucleus of eukaryotic cell
12
Q
G-Banding
A
Technique to produce visible karyotype by staining condensed chromosomes
13
Q
Euchromatin
A
Light-staining, early-replicating, transcribed/translated DNA segments
14
Q
Heterochromatin
A
Dark-staining, late-replicating DNA segments that remain condensed. Includes centromeres, inactive loci, and inactive X chromosome
15
Q
Locus
A
Specific position on a chromosome
16
Q
Allele
A
Alternative forms of a gene or DNA sequence at a given locus. Ex. A, a, B, b
17
Q
Homozygous
A
Both alleles are identical. Ex. AA, aa
18
Q
Heterozygous
A
Different alleles on each chromosome. Ex. Aa, Bb
19
Q
Compound Heterozygous
A
2 different mutant (recessive) alleles at a given locus. Ex. a1a2, Cystic Fibrosis
20
Q
Double Heterozygous
A
One mutant allele at each of 2 different loci. Ex. ab or bc; associated with deafness.
21
Q
Main source of genetic diversity
A
Recombination
22
Q
Recombination occurs during…
A
Meiosis 1
23
Q
Physical distances
A
Base pairs, kilobases, Megabases, etc.
24
Q
Base pairs in human genome
A
3x10^9
25
Genetic distances
Centimorgans (cM). 1 cM = 1/100 meiosis will have a recombination.
26
Genetic mapping
Creating a map by assigning DNA fragments to chromosomes. Based on recombination/meiotic segregation, genetic techniques such as pedigree analysis or breeding experiments
27
Synteny
Physical co-localization of genetic loci on the same chromosome within an individual or species
28
Linkage
< 50% cM, lower than expected recombination frequency between two loci
29
Haplotype
Series of alleles found at linked loci on a single chromosome
30
Physical mapping
Mapping genes or DNA sequences on a chromosome that does not rely on meiotic segregation/recombination
31
Polymorphism
Existence of 2 or more phenotypic variants at significant frequencies in the population. Used as a tool for genetic mapping and testing (diseases, crime, paternity). Underlies genetic diversity, basis for phenotype variability and individual responses to drugs.
32
Genetic marker
A polymorphic DNA or protein sequence deriving from a single known chromosomal location. Can be used to identify individuals or species. Includes RFLPs, microsatellites/VNTRs, SNPs.
33
RFLP
A polymorphic difference in the size of allelic restriction fragments between homologous DNA mlcls as a result of the polymorphic presence or absence of a particular restriction site. A genetic marker.
34
Microsatellites/VNTRs
A genetic marker with many alleles that is highly informative. Can be typed by automated multiplex PCR; easy physical localization, distributed throughout genome.
35
SNPs
A genetic marker that can be types on a very large scale by automated equipment without gel electrophoresis.
Less informative than microsatellites, but may have future use in predicting disease susceptibility, drug responsiveness, "personalized medicine," understanding genetic contributions to complex diseases.
36
% of human genome that codes for proteins
1.3%, < 30,000 genes
37
(T/F) mRNA contains introns and exons
False, only exons
38
Exons encode...
5'-untranslated regions, protein coding sequence/open reading frame, and 3'-untranslated regions
39
of exons and introns in human genes
1 - 178 total exons, avg 8.8 exons and 7.8 introns
40
Average length of exon
145 bp
41
Genomic DNA
Same for given individual in any tissue or developmental stage. Contains regulatory sequences (promoters, enhancers), introns, exons, repetitive sequences (40-45% of genome)
42
cDNA
DNA synthesized from mRNA by reverse transcriptase and DNA polymerase. Different for each tissue and developmental stage in a given individual. Contains mature transcripts (5'-UTR, ORF, 3'UTR, polyA tail), no introns.
43
"Mutant" allele =
Recessive allele
44
(delta)F508 means...
Deletion of phenylalanine at amino acid number 508
45
R1066C means...
Transition from arginine to cysteine at amino acid number 1066
46
Consanguinity
"with blood," indicates a couple that is related. Add 2 horizontal lines on pedigree.
47
To receive info on miscarriages, still births, children no longer living from a patient, ask:
"How many pregnancies have you had?" instead of "How many children do you have?
48
When taking family histories...
Obtain siblings' histories first, then parental family history and medical histories. Doesn't matter whether you choose paternal or maternal first. Should always have 3-generation family history at a minimum.
49
Mendelian Diseases
Diseases that are the result of a single gene mutation
50
Autosomal
Encoded on an autosome
51
X-linked
Encoded on the X chromosome
52
Dominant
Conditions expressed in heterozygotes
53
Recessive
Conditions that are clinically manifest only in individuals homozygous for the mutant allele
54
Punnett Square
Shows probability of progeny with each possible genotype resulting from 2 parents heterozygous for a mutation
55
Autosomal dominant inheritance pattern
Affected individuals give rise to affected progeny, males transmit to both males and females
56
Autosomal recessive inheritance pattern
Unaffected individuals give rise to affected progeny (homozygous recessive), both males and females affected, heterozygotes are carriers
57
X-linked recessive inheritance pattern
Unaffected individuals give rise to affected progeny, typically only males affected (except for rare cases that result from mutations caused by X translocations, extremely skewed X inactivation of the wild type X in a female), can have female carriers.
58
X-linked dominant inheritance pattern
Affected individuals give rise to affected progeny, males transmit only to female progeny
59
Aneuploidy
Abnormal chromosome number, which is not an exact multiple of the haploid number (n = 23). Results from abnormal chromosome segregation during mitosis or meiosis (mostly female meiosis I and risk increases with advancing maternal age), lagging movement of chromosome or chromatin
60
Nondisjunction
Failure of paired chromosomes to separate in anaphase of Meiosis I or failure of sister chromosomes to disjoin at Meiosis II or Mitosis
61
Types of genetic mutations:
Aneuploidy, polyploidy, chromosomal rearrangements, single gene mutations, multifactorial disorders
62
Types of aneuploidy
Trisomies (3 instances of a chromosome instead of 2, most embryonic or fetal lethal), monosomies (embryonic lethal), tetrasomies, etc.
63
(T/F) Aneuploidy of sex chromosomes results in less severe phenotype than that of autosomes.
True
64
Polyploidy
Any multiple of the haploid number of chromosomes (n = 23). Not compatible with survival, observed in small % of spontaneous abortions.
65
Triploidy
Most common polyploidy (3n). Ex. 69XXX, 69XXY, 69XYY. Occurs in 1% of all conceptions, livebirths rare, caused by fertilization by 2 sperm, error in maternal meiosis II.
66
Chromosomal rearrangement
Results from chromosome breakage or recombination between mispaired chromosomes during meiosis. 1/1000 infants born with symptomatic chromosomal rearrangement, non-symptomatic rearrangements often account for infertility/miscarriages.
67
Types of chromosomal rearrangements
Deletions (loss of part of a chromosome, contiguous gene syndromes), translocations (part of chromosome is transferred to another, only causes disease when break is within important gene or copy # of gene is changed), inversions, formation of ring chromosomes
68
Types of translocations
Balanced reciprocal translocation (equal size portions transferred, few symptoms but may have infertility. DNA not lost usually.), Robertsonian translocation (fusion of q arms of 2 acrocentric chromosomes, considered balanced since lost p arms contain only repetitive arrays of rRNA genes)
69
46XX means...
Normal female
70
46XYt(3;11) means...
Male with balanced translocation, chromosomes 3 and 11 abnormal about 75% of the time
71
46XYder(14;21)
Male with Robertsonian translocation between chromosomes 14 and 21.
72
Types of single gene mutations
Point mutations, deletions (large ones can lead to contiguous gene syndromes, can cause frameshift), insertions (can cause frameshift), mutations (in regulatory regions, <1% of disease causing mutations, can be silent or have minor effects on protein expression), mitochondrial mutations (maternal inheritance pattern)
73
Point mutations
Change in single base pair, 60% of disease causing mutations
74
Types of point mutations
Transition (purine replaced by another purine), transversion (purine to pyrimidine or v.v.), missense mutation (generates amino acid change), nonsense mutation (generates premature stop codon), synonymous or silent base change (no resulting amino acid change), splice site mutation (changes in intron-exon junction or intron branch site)
75
Multifactorial disorders
Also called polygenic disease or complex diseases; caused by interacting genetic and environmental risk factors, not a single major mutation; encompasses most common diseases (diabetes, cardiovascular diseases, allergies, susceptibility to infection diseases)
76
X inactivation
In females, one X chromosome is randomly inactivated - normally 50:50, very rarely 90:10.
77
(T/F) Inactivating an autosome is not compatible with life.
True. Cannot inactivate autosome even if X chromosome was translocated onto it.
