THEME 5 MOD 1 Flashcards
T OR F:
exons and introns (protein coding regions) make up the human genome
False: they make up a small part of the human genome
sequences contributing to genetic variation across organisms
- tandem repeats: up to several 1000 nucleotides in length, present next to eachother in near identical copies
- simple repeats: repeats of as little as 2 nucleotides
- non coding rna regions
- single copy genes
does all sequence variation in the genome have an observed effect?
No, sequence variation presenting in non protein coding regions have no observed effect
outcomes of variation depend on their nature and where they occur
What is a purpose of genome sequencing projects
map out chromosomes with high resolution to determine underlying dna sequences and annotate them to provide insight on mechanisms of inherited disease and genetic variablility
DNA polymorphisms
- 1 or two alternative forms that differ in one nucleotide or in number of tandem repeats (alleles) within a chromosmal region (locus)
- large number of dna polymorphisms across genomes of many organisms, mostly present in non coding regions
- used as dna markers for high density genetic maps
- detectable by microarray analyses, pcr, southern blot, or dna sequencing
- can display relatedness and identify people
How similar are human genomes
99.9% the same
accounts for observed genetic variation
what is important about SNPs and genetic variation
- most common form of genetic variation
- caused by single nucleotide base change
- occur in signifigant amount of the population in coding and noncoding regions
- occurs in roughly 1 in every 350 base pairs, meaning there is possibly millions per an individual genome
- SNPs close to a gene can be used as dna markers for that gene
- if an snp is close enough to a specific gene, it will be passed on through generations
analyzing SNPs through micro array analysis
- oligonucleotides matching the allele and ones with all possible SNP alleles (nucleotide base in the middle complementary to SNP) are attached to the glass chip
- fluorescently labelled DNA fragments of individuals are hybridized to the chip
- match the oligonucleotide probe (of known placement) to the fluorescing pattern to identify which SNP a person has and whether its homozygous or heterozygous for each SNP
How researchers determine which SNP allele an individual has?
- Detecting for two possible snp alleles: A-T and C-G
- Each snp allele will have a certain pattern of fluorescing
- Fluorescent pattern on the microarray chip will reveal whether an individual is homozygous for A-T, C-G, or heterozygous for A-T/C-G
SNP profile
- Every individual has a unique pattern of SNPs
- Variations don’t necessarily effect gene function or cause disease, they just serve as markers of an individuals genome
What are VNTRs
variable number of tandem repeats, contribute to genetic variation
tandem repeats: repeat of one or more nucleotides adjacent to each other in varying lengths and repeat numbers in different individuals
How can VNTRs be identified
- by PCR and gel electrophoresis
-tandem repeat sites are targeted and amplified by primers that target flanking regions of the tandem repeats - amplified dna can then be sorted and visualized by gel electrophoresis
- detecting VNTRs of different lengths can help researchers idetify persons by their genetic profile
explain dna fingerprinting
examine VNTR loci (locations) to identify an individual because while related people have similar placement, they vary enough that no two individuals should have the same VNTRs
what makes up a persons genetic profile
- polymorphisms and VNTRs ‘markers’
silent variations
variations of genome with no known effect because they occur in non coding regions
what happens when there is a variation in a protein coding or regulatory region of DNA
production of an altered gene product which can be detrimental
Explain the relationship between sickle cell anemia and genetic variation
- sickle cell anemia caused by specific variation of a gene sequence passed down from parent to child
- RBC have an abnormal phenotype: sickle shape, due to variation of hemoglobin protein
Physiological phenotype of sickle cell anemia
- sickle shape red blood cells which can lodge within fine capillaries causing anemia and acute pain
- cannot transport efficient amount of oxygen to the body
- damage occurs in tissues and organs
specific variation of the human genome leading to sickle cell anemia
- gene for beta globin protein lies on an autosome (two alleles), chromosome number 11
- people with smooth, biconcave RBC and normal oxygen affinity are homozygous for the HbA allele, one from their mom and dad
- people homozygous for the HbS allele cannot make functional beta globin proteins
- HbS allele caused by a single nucleotide polymorphism causing the switch of one amino acid from a glutamine to a valine, alternating the tertiary structure of the protein
- this single nucleotide polymorphism in both alleles causes a decreased ability to bind to oxygen and a biochemical change at the protein level aggregating the abnormal beta globin protein, resulting in rod like structures in the cell forming the sickle shape
What is the outcome of someone with one HbA and HbS allele
- will develop some sickle cell properties, as some beta-globin will be sickle cell beta hemaglobin
- the rest of the beta hemoglobin protein will be normal, and the person wont exhibit symptoms of sickle cell anemia
- these heterozygotes produce enough normal beta hemoglobin to overcome the effects of the abnormal hemoglobin
Other than identification, why is dna finger printing advantageous?
- can conduct large scale population genetic analyses
findings of global analyses of epidemiology as it relates to sickle cell anemia
- in some regions, heterozygous for the sickle cell anemia is advantageous and leads to resistance to malaria in regions with malaria threats
- sickle cell mutations found in many populations with different alleles/haplotypes
- 5 distinct beta hemoglobin haplotypes found across patients correlating to regional distrubiton of the single nucleotide polymorhpisms
- regions studied had advantageous heterozygote for sickle cell anemia that made them resistant to malaria
What are CNVs
gene copy number variations, contributing to genetic variation
can occur in coding or noncoding regions
a gene typically present in one copy per chromosome may be duplicated, deleted, or multiplied
can detect CNVs by strength of fluorescent of an area of a chromos during microarray analyses
duplications usually occur adjacent to eachother along a chromosome
What is an example of CNVs
Copy number of the AMY1 gene! copy number is a direct reflection of selective pressures (how much starch ancestors consumed?)
