Study Heredity Basics and Inheritted diseases and Disorders Flash Cards

 
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Heredity Basics and Inheritted diseases and Disorders

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Hello, Dolly!
1997—Dolly became the first of many cloned animals resulting from somatic cell nuclear transfer
Ribozymes
-discovered in 1981
-provided novel way of preventing unwanted gene expression (ex:
cancer and AIDS)
Altman and Cech
awarded Nobel Prize for their
discovery of ribozymes
first recombinant vaccine
to Hepatitis B
was developed in 1987
Human Gene Therapy
-approved in 1990
-ADA deficiency treated with lymphocytes engineered with
retroviral ADA gene
-responses were positive but
efficacy could never be proven
-SCID X1 treatment was effective, but resulted in 2 children developing leukemia
HGP fun facts
-Human genome comprised of only 30,000 genes
-Proteome may explain difference in complexity of organisms
-Most common type of DNA sequence is SNP
-Hundreds of human genes originated from horizontal
transfer from bacteria or have evolved from transposable elements
Two different strategies HGP strategies
Celera Company (Craig Venter)
-Used shot‐gun approach
-blasted the genome into small fragments, each sequenced individually, then used computer software to align
-faster, but less accurate
Two different strategies HGP strategies
-DOE/NIH (Francis Collins)—many labs throughout the world carefully sequenced each base in the
segment of DNA they were allotted
-Parallel projects were completing sequences of smaller genomes
Initial goals of the HGP
-Mapping & sequencing human/model organisms genome
-ID 30,000 genes
-Software & database development
-transfer technology to private sector
Human Genome Project
-Began as government funded joint project by DOE (for nuclear weapons) and NIH
-not just “human” DNA
making human genome map...
-variability of polymorphisms led Jeffreys et al to propose a method of DNA fingerprinting
-produce unique profiles to ID humans
-SNPs were proposed as means to produce genome map
Mutation Detection
-Direct detection through sequencing
-preferred method
-expensive!
-Other methods to detect mutations: DNA scanning, linkage analysis
SNP
-Single Nucleotide Polymorphism
-Potentially the most useful
-difficult to detect because they may not alter the recognition
sequence, or the length of the restriction fragment
-used in gene discovery research to
ID small differences which may result in
significant phenotypic variabilities
-$$$
SSR
Simple Sequence Repeats (also called microsatellites)
-much smaller
-can only be detected by PCR
-small repeats make fragments different lengths
VNTR
-Variable Number of Tandem
-potentially more informative, as there are more possible variants
-the restriction fragments would vary
in size based on the difference in the number of repeats
RFLP
-Restriction Fragment Length Polymorphism
-segment of DNA is digested by restriction enzymes
-the resulting fragments will be varying
lengths, due to the differences in recognition sites
Polymorphisms
-Most changes in DNA don't lead to disease
-the majority do not effect function, unless it falls in regulatory region (controls expression)
-RFLP
-VNTR
-SSR
-SNP
DNA Mutation Terminology
-Δ means deletion; ex: ΔF508 is a deletion of the amino acid phenylalanine at position 508
-Cys282Tyr means there is a cysteine to tyrosine substitution at position 282
-use single letters instead
Clinical phenotypes of chromosomal abnormalities
-Developmental delay/mental retardation
-facial morphogenesis
-Growth delay
-Congenital malformations, especially heart defects
Ring chromosome
material is deleted at both ends, the new ends join to form a ring
Duplication
section of chromosome is duplicated
(extra genetic material)
Inversion
section of chromosome is snipped out and reinserted upside down
Translocation
section of chromosome attached to another chromosome
Microdeletion
minute amount of material is missing
Deletion
small section is missing
Chromosomal Structure Abnormalities
Deletion
Microdeletion
Translocation
Inversion
Duplication
Ring chromosome
Klinefelter
2 or more X chromosomes w/Y
Triple X
extra X chromosome
Turner Syndrome
missing all of part of one X
Edwards Syndrome
Trisomy 18
Patau Syndrome
Trisomy 13
Down Syndrome
Trisomy 21
Abnormality of Number
Abnormal meiosis‐ cells divide abnormally, resulting in sperm or egg cells with too many or too few
chromosomes
Sister chromatids don’t separate properly → resulting
cells abnormal
One cell has too many chromosomes → trisomy
One cell has too few chromosomes → monosomy
Chromosomal Abnormalities
Abnormalilities of number
-Polyploidy
-Aneuploidy

Abnormalities of structure
-Deletions
-Microdeletions
-Translocations
-Inversions
-Duplication
-Ring chromosome
SKY
Spectral Karyotyping
FISH
-Fluorescence in situ hybridization
-greater resolution of chromosomes
-fluorescently labelled probes used to identify specific loci on chromosomes
Useful in identifying chromosomal abnormalities:
numerical (aneuploidies & polyploidies), structural
(translocations, deletions) & mixtures (mosaicism)
chromosome regions
-chromosomes (p and q) are divided into regions
-IDs specific genes locations
EX: 7q31.3 = chromosome 7, long
arm, region 3, band 1, sub‐band .3
G‐banding
-banding pattern from giemsa staining
-IDs each chromosome
Karyotype
the chromosomal makeup (number, size
and morphology) in a cell, individual or species
Cytogenetics
the study of chromosomes
giemsa staining banding pattern
-euchromatin stains lighter
-heterochromatin stains darker
chromosome structure
Double Helix →
Nucleosomes →
Chromatin →
Chromatids
telomere
tandem repeats
Centromere
-divides chromosomes into short (p for petite) and long (q for not p) arms
PCR Problems
-very sensitive
-minute amounts of contamination can be amplified
-fidelity of polymerases‐ error rate is ~ 1 nucleotide/400 bases
-old/decaying samples
-LCN PCR can lose sequence
specificity
Q‐PCR
-Quantitative PCR
-allows products to be measured in real time
In Situ PCR
‐allows genes or mRNA to be amplified from tissues (used to identify tissue‐specific genes)
Multiplex PCR
‐uses several sets of primers in one
reaction (this is used on forensic DNA analysis)
RT‐PCR
-Reverse Transcriptase PCR
-uses RNA as a starting product
copies made by PCR
2^n
Taq polymerase
-heat resistant
PCR Steps and Temps
Denaturation‐ 94
Annealing‐ 59
Elongation‐ 72
When/who developed PCR?
developed in 1985 by Mullis, Saiki and colleagues at Cetus Corporation
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