Term
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Definition
| combination of multiple genes |
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Term
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Definition
| a type of genetic defect that can be visualized via cytogenetics |
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Term
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Definition
| a type of mutation in germ cells that are passed on to the offspring and incorporated into all of their cells |
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Term
| Somatic Cell Genetic Defect AKA sporadic mutation |
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Definition
| a type of genetic defect that is caused by change in somatic cell, not transmitted to offspring, may occur after environmental exposure, or spontaneously due to a DNA repair defect |
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Term
| Haplotype AKA haploid genotype |
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Definition
| a collection of single nucleotide polymorphisms that are inherited together on the same chromosome. They represent genetic markers that are closely linked. SNPs may be located at coding or non-coding sites. The pattern of a haplotype is used in genetic association studies of complex diseases. |
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Term
| Steps in how a molecular defect can cause a disease |
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Definition
| Gene is lost or mutated modified protein product varying phenotype |
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Term
| When do somatic mutations often arise? |
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Definition
| Somatic mutations often arise when proofreading or repair enzymes are defective resulting in a permanent change |
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Term
| Diseases caused by a point mutation |
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Definition
Sickle Cell anemia
Alpha thalassemia
Li-Fraumeni cancer syndrome (defect in p53) |
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Term
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Definition
| caused by a point mutation that changes the codon coding for glutamic acid to valine |
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Term
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Definition
| a point mutation at a stop codon [UAA->CAA(glutamine), UAA->UCA(serine) UAA->UAU (tyrosine) will cause the encoded protein to have extra amino acids. An alternative in-frame stop codon located 31 amino acids downstream will be utilized. Globin protein usually unstable. |
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Term
| WHat are other mutations associated with alpha-thalassemia that can affect RNA processing? |
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Definition
(a) poly(A) recognition sequence in alpha 2 globin gene will affect mRNA stability,
(b) Splice-site mutations will affect mRNA transcript length.
c)can be caused by deletions in the alpha chain nucleotides, which alters alpha globin synthesis and can cause fetal death (fetal development altered in utero) |
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Term
| Effects of p53 gene mutations |
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Definition
can cause the development of sporadic cancers in which the mutations,found in the tumor suppressor region, are only found in the tumor DNA.
People with this defect have a rare autosomal dominant defect called Li-Fraumeni cancer syndrome |
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Term
| What can a point mutation nucleotide change within the promoter region lead to? |
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Definition
| . A nucleotide change within the promoter sequences of a gene can lead to either lower or greater gene expression levels |
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Term
| Deamination of methyl cytosine can result in... |
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Definition
| change of CpG to TpG nucleotide. |
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Term
| Other changes that are associated with point mutations due to methylation of a nucleotide in the DNA promoter sequence... |
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Definition
results in lower or absent gene expression.
Example: . The p16(produces a tumor suppressor protein) and DNA mismatch repair genes are examples where excess methylation of promoter sequences at CpG sites in some tumors have been associated with absent or a severe reduction in transcription. |
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Term
| Nucleotide change at a splice site can cause..... |
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Definition
| Splice site mutation in COL1A2 gene will result in loss of exon 6 leads to Ehlers-Danlos Syndrome. |
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Term
| Where might mitochondrial genome point mutations be located? |
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Definition
| point mutation may be located in tRNA, rRNA or one of the 13 protein encoding genes. |
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Term
| Point mutatuion in the mitochondrial 12S rRNA can lead to.... |
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Definition
alterations in the stem-loop structure, which is believed to increase its binding to some antibiotics
results in familial antibiotic induced deafness
Examples of antibiotics: kanamycin, neomycin |
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Term
| Disorders associated with the deletion of an entire structural gene |
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Definition
Hemophilia
Beta-Thalassemia |
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Term
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Definition
| a disease that occurs when the entire Factor VIII gene is removed |
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Term
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Definition
Splice site mutation caused by deletion of one or more beta-globin genes and affects mRNA processing. Disease severity depends on number of genes deleted. The disease will be lethal if both beta-globin genes are deleted, while a mutation in one of the beta-globin genes will result in a milder disease (microcytic anemia).
Thalassemia results from an imbalance in the synthesis of alpha and ß-globin chains. |
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Term
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Definition
| A milder form of Beta thalassemia that is caused by a mutation in which only one of the beta thalassemia genes are deleted |
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Term
| Diseases causesd by a partial deletion of a gene |
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Definition
Duchenne muscular dystrophy
Becker muscular dystrophy |
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Term
| What is the gene responsible for DMD and BMD? |
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Definition
| Gene responsible is dystrophin (located on chromosome X; X-linked pattern of inheritance) |
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Term
| What type of partial deletion/insertion causes DMD? |
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Definition
| more severe than BMD causes an out of frame mutation |
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Term
| What type of partial deletion/insertion causes BMD? |
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Definition
caused by an in-frame deletion/insertion less severe than DMD
Exon duplication is associated with 5% of cases |
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Term
| What disease is caused by codon deletion? |
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Definition
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Term
| What specific gene mutation is causes cystic fibrosis? |
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Definition
Mutation in the chloride ion channel called, cystic fibrosis transmembrane regulator (CFTR).
More specifically,the most common mutation involves loss of an amino acid (phenylalanine) at codon position 508 due to CTT deletion
PCR is used to detect this disorder |
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Term
| What disease is associated with a frameshift mutation? |
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Definition
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Term
| What is a frame shift mutation? |
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Definition
| : Insertion or deletion of nucleotides will cause a shift in the reading frame during translation of mRNA. A random amino acid sequence will occur on the carboxyl side of the mutation that could result in a truncated protein caused by the introduction of a premature stop codon. |
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Term
| Tay-Sachs disease is due to ..... |
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Definition
| to a 4-nucleotide insertion that results in a defective hexosaminidase. |
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Term
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Definition
| 1 gene influences many phenotypic traits |
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Term
| How can the knowledge of a haplotype be used? |
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Definition
| Haplotype may be used in personalized medicine, and to test genetic associations with diseases. |
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Term
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Definition
Caused by a point mutation that results in the loss of a proteolytic cleavage site.
This prevents the inactivation of Factor Va and leads to excessive clotting.
Associated with deep vein thrombosis |
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Term
| What results when there is a loss of DNA methylation? |
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Definition
Highly methylated CpG DNA regions will adopt a condensed chromatin conformation.
5’-Methylcytosine is chemically unstable and prone to spontaneous deamination forming thymine.
Thymine is not recognized by nuclear DNA repair machinery as abnormal, which leads to a loss of gene expression control. |
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Term
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Definition
Type VII A & B are caused by a point mutation that prevents post-transcription processing.
This causes a loss of exon 6 in the COLIA2 gene thst encoded for alpha-2 chain of procollagen
This autosomal dominant mutation prevents proteolyitc processing. |
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Term
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Definition
occurs when a nucleotide change results in a change in amino acids which could possibly lead to the formation of an oncogene
THis is an example of a ras mutation and can occur in someone that is a smoke. |
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Term
| Myoclonus Epilepsy Associated with Ragged-Red Fibers (MERRF) |
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Definition
| caused by a mutation in mitochondria tRNAlys. |
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Term
| MELAS (Myopathy encephalopathy lactic acidosis and recurrent stroke-like episode) |
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Definition
caused by a mutation in mitochondria tRNAleu.
Pyruvate can no longer be oxidized, so the pyruvate is converted to lactic acid. |
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Term
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Definition
| Amino acid will change if polymorphism occurs in coding sequence |
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Term
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Definition
nucleotide substitutions
nucleotide deletions/insertions
tandem repeats,trinucleotide repeats, and CNV |
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Term
| disorders caused by Polymorphic Triplet repeats AKA trinucleotide repeats |
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Definition
Fragile X
Myotonic Dystrophy
Huntington's |
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Term
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Definition
a mutation in the number of trincleotide repeats that is associated with FMR-1 gene.
Defect can be detected as a region of incomplete condensation in metaphase chromosomes under special culture conditions |
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Term
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Definition
Pre-mutations repeats can be meiotically unstable and offspring can have an expanded number of trinucleotide repeats
Refer to slide 23 about fragile X |
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Term
| What can be used to identify family members? |
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Definition
| Southern Blotting of minisatellites AKA short tandem repeats |
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Term
| What is microsatellite Instability caused by and by what methodis it detected? |
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Definition
MSI is due to a defective mismatch repair (MMR) gene in certain cancers. Approximately 13% of colorectal, gastric and endometrial carcinomas have a defective MMR gene.
Can be detected using PCR amplication |
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Term
| AN example of insertion of sequences within a gene. |
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Definition
| • Insertion of mobile or “jumping” Alu elements into coding sequences will be lethal. |
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Term
| Partial Gene Duplication and DMD and BMD |
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Definition
| causes disruption of exon organization: duplication of specific exons (5% of cases of DMD/Becker MD). |
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Term
| Multi-Stage Development of Colon Cancer |
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Definition
1. normal intestinal epithelium
2. aberrant crypt focus
3. adenoma (early, middle, and late)
4. carcinoma |
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Term
| Tumor Suppressor gene can be silenced by: |
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Definition
1. Partial gene deletion or loss of sequences that is observed as loss of heterozygosity (LOH).
2. Point mutation.
3. Epigenetic defect like CpG islands/sites in the promoter is a substrate for methylation or Hypermethylation is related to a reduction in transcription. |
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Term
| How can Loss of heterozygosity be determined? |
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Definition
| can be determied using southern blotting and must be compared to a normal sample. will appear as a loss of a band |
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Term
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Definition
| this is how deletion of the Rb gene is detected by cytogenetics |
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Term
| Mosaics and Post-zygotic mutations |
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Definition
Mosaics have Two (or more) Genetically Different Cell Lines
Post-zygotic mutations produce distinct cell lines that have either different sets of chromosomes or different gene mutations for a single gene in different cells.
E.g. DM1 gene locus (myotonic dystrophy type 1)- range of somatic CTG expansion in different tissues; may increase with age. |
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Term
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Definition
| Any multiple of the haploid number of chromosomes, e.g., 3N, 4N (common in spontaneous abortions). |
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Term
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Definition
Change in the number of one chromosome.
Examples: Autosome, e.g., trisomy 21 (Down syndrome)
Sex chromosome, e.g., Klinefelter’s syndrome (47,XXX); Turner syndrome (45,X0). |
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Term
| Spontaneous Fetal Loss for Autosomal Trisomies |
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Definition
| Less than 50% survival rate of trisomy 21. Poor survival of trisomy 13 (Patau syndrome) and 18 (Edwards syndrome) conception, but no survival of trisomy 16. |
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Term
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Definition
Both copies of a single chromosome (or major part of that chromosome) is inherited from the same parent. The other parent contributes nothing to that portion of the embryo’s genome.
Mutations to genes located on Y chromosome.
Examples: Beckwith-Wiedemann, Prader-Willi and Angelman syndromes |
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Term
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Definition
| When both copies of a autosomoal chromosome are inherited from one parent and the copies are the same |
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Term
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Definition
| When both copies of a autosomoal chromosome are inherited from one parent and the copies are different |
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Term
| Types of structural defects |
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Definition
1. Micro-deletions/contiguous gene syndromes
2. Translocation
3. Inversions, insertions, and duplications
4. Interchange between X and Y chromosomes |
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Term
| Micro-deletions/contiguous gene syndromes |
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Definition
a specific region of the chromosome is deleted.
Examples: Angelman/ Prader-Willi denoted as: del (15) (q11q13) |
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Term
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Definition
| Burkitt's lymphoma is due to a translocation between the long arms of chromosome 8 and 14. |
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Term
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Definition
Flourescent in situ hybridization. can be used to examine 2 or 3 probes simulatenously
Can only detect chromosomal aberrations NOT DNA base pair mutations |
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Term
Detection of Mutations
Southern Hybridization/Fragment Length Polymorphism (RFLP) |
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Definition
RFLP exploits the differences in DNA sequences from different individuals by the use of restriction endonucleases. Restriction endonucleases cleave DNA only at specific recognition sites (palindrome). When a single base pair mutation occurs at a homologous site (in an allele), the sequence is no longer a "recognition site" and the DNA is not cleaved. The separated DNA fragments will always appear 'co-dominant,' unlike a biochemical assay where an enzyme level is measured.
Technique may be used to detect tandem repeat sequences, exon deletion or duplication (assuming these regions are flanked by a restriction site).
Example SS anemia by the use of MstII |
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Term
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Definition
| useful when only small amounts of DNA are available. PCR-RFLP involves a combination of DNA amplification of a fragment of a gene under study, followed by digestion with a restriction enzyme. |
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Term
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Definition
| chromosomal translocations |
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Term
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Definition
Insertion of Chromosomal Region |
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Term
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Definition
Structural Chromosomal Mutations |
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