Lecture 1: Intro to Genetics Flashcards
Genetics
study of biologically inherited traits determined by elements of heredity (genes) transmitted from parents to offspring in reproduction
-genetic information helpful to maintain head, facilitate diagnosis of illness and solve problems assoc. with human diseae
Genomics
functions and interactions of all the genes in the genome
Types of genetic disorders (4)
- Chromosome d/o
- single-gene d/o
- multifactorial d/o
- mitochondrial d/o clinically heterogeneous
Chromosome genetic disorders (3)
- numerica/structural abnormalities
- down syndrome (trisomy 21)
- Turner syndrome (complete or partial absence of second X)
Single-gene genetic disorders (3 ex.)
- hemophilia
- cystic fibrosis
- sickle cell anemia
Multifactorial disorders (3 ex)
- diabetes
- heart disease
- cancer
Mitochondrial genetic disorders (3)
- mitochondrial (mtDNA) or nuclear DNA
- Leber hereditary optic neuropathy (LHON)
- Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS0)
Central Dogma Molecular Biology
DNA
transcribed *** into RNA
RNA
translated*** into protein
DNA (3)
- double stranded structure that contains genetic code
- strand-like macromolecule of numerous nucleotides (nt)
- bases are carriers of genetic information, letters to genetic test
Nucleotides (2)
- composed of base + sugar + Phosphate groups
2. sugar and phosphate groups give the macromolecule its structure (sugar-phosphate backbone)
Nucleotide Bases
2 types
- momoneric units of deoxynucleic acids
- Purine bases
- Pyridine bases
Purine Bases
- Adenine
- Guanine
“PUR As Gold”
Pyridine Bases
- Cystosine
- Uracil* in RNa
- Thymine
“CUT the Py”
Bonds in DNA base pairs (2)
- hydrogen, hold DNA strands together
2. base pairing occurs between a purine and pyrimidine
Chargaff’s rule
A=T
C=G
Phosphodiester Bond (4)
- Bond that forms backbone of DNA
- bone between adjacent nucleotides
- between the phosphate on one nucleotide and the 3’-OH on the next nucleotide
- chain of nucleotides has a 5’-3’ orientation
Complimentarianism in DNA
Base pairing allows DNA to be complementary
-allows one DNA string to serve as a template for the synthesis of the other strand
DNA replication
Central Dogma factor
- replication forms identical DNA molecules during cell division
RNA Transcription
Central Dogma factor
- transcription refers to the formation of complementary RNA molecule (mRNA) using DNA as a template
- Ribose- uracil instead of thymine *
Protein
Central Dogma factor
- language of nucleic acid translated into a polypeptide sequence through specialized transfer RNA (tRNA) molecules that contain the specific RNA sequence that is complementary to RNA and also caries a specific amino acid
DNA and chromosomes (2)
- DNA packed into chromatin
2. highly condensed chromatin is visualized as chromosomes
Cromatin (2)
- made up of DNA, protein, and some RNA
- visualized as chromosomes when highly condenses
- packaging of chromatin varies depending on the activity of the cell
Chromosomes
means by which the genes are transmitted from generation to generation
Function of chromatin (4)
- Package DNA into a compact shape so that it fits into the nucleus of a cell
- reinforce the strength of the DNA molecule to allow for mitosis
- prevent DNA damage
- Allows control of processes like gene expression an DNA replication
Human Chromosomes (2)
- genome of a diploid cell is distributed in 46 chromosomes
- 23 pairs
- 44 autosomal and 2 sex - Genes are arranged linearly along each chromosome
How many autosomal chromosomes
44
sex chromosomes
2
Gene
DNA sequence that encodes the structural compound of a gene product plus regulatory sequences
Locus
specific chromosomal location
ex) eye color on one spot of a chromosome
Allele
homologous copy of a gene
mtDNA
purpose
mitochondrial DNA
-encodes proteins or oxidative metabolism and all tRNAs used in translation of proteins within this organelle
Mutation
a change in DNA the may adversely affect the host
Groups of mutations (3)
- numerical chromosome abnormalities
- structural chromosome abnormalities
- gene mutations that alter the function of individual genes
Types mutations (2)
- Germinal Mutations
2. Somatic mutation
Numerical Chromosome Abnormalities (4)
- changes the total number of chromosomes (aneuploidy)
A. arise from nondisjunction (faulty segregation of chromosomes in meiosis or mitosis)
B. Monosomy, Trisomy, Polysomy
C. Always clinically evident, as a full, they are de novo (NOT INHERITED)
Aneuploidy
changes the total number of chromosomes
nondisjunction
faulty segregation of chromosomes in meiosis or mitosis
Structural chromosome abnormalities
2 types
- balanced
2. unbalanced
Balanced structural chromosome abnormality
structural abnormalities involve no loss of gain in chromosomes-not evident clinically
Unbalanced structural chromosome abnormalities
2 characteristics
chromosome abnormalities involve a gain or loss of chromosome segments and are clinically relevant
- can be passed on from generation to generation
- duplications, deletions, inversion, and translocations
Gegor Mendel
1st to describe inheritance
Mendel’s 1st law of genetics
- law of segregation : allele pairs separate or segregate during gamete formation and randomly unite at fertilization
- one member of the gene pair segregates into a gamete, each gamete carries only one member of gene pair
Dominant Genes
the allele that expresses itself at the expense of an alternate allele
-phenotype that is expressed in the F1 generation from the cross of 2 pure lines
Recessive Genes
an allele whose expression is suppressed in the presence of a dominant allele
-phenotype that disappears in the F1 generation from the cross of two pure lines and reappears in the F2 generation
Gamete (2)
- carries one member of the gene pair
2. unite at random and irrespective of the other gene pairs involved
Principle of Independent Assortment
during gamete formation, segregation of the alleles of one allelic pair (shape) is independent of the segregation of the alleles or another allelic pair (color)
*excp: to this rule occur when genes are linked, or positioned very closely together on a cromosome
Dihybrid cross
crossed organism differing in 2 characters
Genotype
Genetic makeup
Phenotype (3)
- observable results
a. some genes have no outward effect on organism
b. expression can depend on environmental factors such as diet
Effect of mutation
may be ameliorated or exacerbated by external factors
Punnet Sq. (3)
- easy tool for basic estimate of inheritance pattern and risk
- can clarify situation visually
- need to know genotypes and inheritance pattern
Autosomal Dominant inheritance (6)
- gene positioned on non-sex chromosome
- successive generations affected (vertical transmission)
- no “skipped” generations - one parent should be affected
- Males and females affected with equal frequency and severity
- disease transmitted to subsequent generations by females as well as males
- Approx. 1/2 of children will be affected
Autosomal Recessive Inheritance (5)
- occurs only in one generation, not successive
- affects males and females with equal frequency and severity
- Generally rare in population
- 1/4 normal, 1/2 carriers, and 1/4 affected
- higher frequency in the offspring of consanguineous couples (1st cousin marriage)
Pedigree analysis (3)
can determine mode of inheritance for traits
- represents familial relationships among biological relatives
- used to determine mode of inheritance for phenotypic traits or disease
- all affected and unaffected individuals in the family are recorded in flow diagram (pedigree) using standard symbols
Pedigree (3)
- include at least 3 generations
- age, relationship, disease, status, age at death, etc.
- of particular importance are similarly affected siblings, miscarriages, stillbirths
Typical Pedigree of Autosomal Dominate Disorder (5)
- vertical pattern observes in pedigree-multiple generations are affected
- heterozygotes for the mutant allele show and abnormal phenotype
- males and females are affected with equal frequency and severity
- only one parent must be affected with equal frequency and severity
- only one parent must be affected for an offspring to be a rx for developing phenotype
Cystic Fibrosis Mutations
Ex. of autosomal recessive disorder
- mutation in cystic fibrosis transmembrane conductance regulator
CFTR gene - delta-F508 most common mutation (70% of while CF patients)
- other rare mutations discovered
X-linked inheritance patterns (8)
- daughter’s inherit father’s X in addition to one copy mother’s X
- Son’s inherit father’s Y and one X from mother
- Rx of inheriting mutant x-linked disease is different for males and females
- there is no male-to-male transmission of phenotype
- unaffected males to not transmit phenotype
- all daughters of an affected male are heterozygous carriers
- males are usually more severely affected than females
- whether a heterogygus female is counted as affected and whether the phenotype is called “recessive” or “dominant” often depends on the sensitivity of the assay or examination
X linked d/o example
hemophilia
Mitochondrial inheritance patterns
- human zygote received almost all of its mitochondria from the oocyte
- during fertilization only the head of the sperm, without mitochondria penetrates the egg - passed by female to all of her offspring (including males)
- Males do NOT transmit mutation
Typical Pedigree with mitochondiral disorder
2 exceptions
ex) MELAS Syndrome= Mitochondrial Encephalopathy, Lactic Acidosis, and Strokelike episodes
ex) MERRF Syndrome- Myoclonic Epilepsy with Ragged Red Fibers
Dx techniques in Medical Genetics
- Family hx and pedigree
- Cytogenetic studies
- Fluorescence in situ hybridization (FISH)
- DNA Analysis
- Biochemical Analysis
Family Hx and Pedigree
- inquire as to present ages, sex, ethnicity, general health, status, major illnesses (chronic, cancer), causes of death and ages of death and age when first diagnosed
- should be collected on all 1st degree relatives (3 generations ideal)
- construct pedigree and evaluate for patterns of prevalence
Cytogenetic Studies show gross chromosomal changes
3 components
- utilizes light microscopy
- cells grown in tissue culture, mitosis is chemically inhibited before staining, photographing, sorting, and counting the chromosomes is performed
- suitable samples included peripheral blood, amniotic fluid, trophoblastic cells from chorionic villus (umbilical cord), bone marrow, cultures fibroblasts (skin bx)
FISH (2)
Fluorescence in Situ Hybridization
- combines cryogenic and molecular genetic approaches showing chromosome segments in color under fluorescence microscope
- Locus-specfic DNA probes allow reliable detection of small microdeletions that are not visible in traditional G-banded chromosome lysis
DNA analysis
- DNA from patient combined with primers in a reaction miscture that replicates and amplifies DNA through process called polymerase chain reaction
- after PCR, amplified products can be examined with respect to sequence size and quantity
Polymerase Chain Reaction
PCR
DNA amplified
*can be used to detect HIV my amplifying DNA or portion of viral genome
Examples of indications for DNA analysis
- screening for cystic fibrosis
- thalassemia
- hemophillia
- familial polyposis coli
Genetic testing for CF (3)
- gel electrophoresis
- separates DNA fragments by Size
- molecules to be separated are pushed by an electric field through a gel that contains small pores - shorter runs faster
Biochemical Analysis for Detecting Genetic Diseases (4)
- Used to determine presence or absence of certain proteins (products of genes)
- ID protein characteristics and effectiveness in vitro
- used to look for enzymatic defects
- Phenylketonuria (PKU) testing detects deficiency/absence of phenylalanine hydroxylase
