Trans - Basic Principles of Clinical Genetics Flashcards
Number of genes in humans
30,000
Number of base pairs in human genome
31,647 billion base pairs
Percentage of genes coding for proteins
less than 2%
Percentage of junk DNA in genome
as much as 90%
_____% of bases are exactly identical in all people
99.9%
Disease status is influenced by: ___ [2]
[1] genetic factors;
[2] environmental factors
Epigenetics
Study of heritable changes in gene expression caused by chemical modifications in a chromosome
3 interrelated mechanisms involved in epigenetics
[1] DNA methylation;
[2] histone modifications;
[3] activity of miRNA
Significance of miRNA activity in epigenetics
[1] miRNAs are encoded within the genome;
[2] miRNA expression is regulated by other epigenetic mechanisms;
[3] miRNAs bind to specific 3’ UTR of an mRNA, and inhibits translation to protein
Characteristics of open chromatin
nonmethylated DNA, histones with acetylated tails
Mediates DNA methylation
DNA methyltransferase
What heavily influences an individual’s adult health?
Early prenatal factors (exposure to certain substances, etc.)
Effect of foliate or choline deficiency in mother’s diet
Undermethylation of certain portions of fetal DNA –> abnormalities
What is BPA and what is its effect on agouti mice?
Exposure to BPA (Bisphenol A) during early development causes decreased methylation of the agouti gene
The family pedigree is a tool for: [6]
[1] Making a medical diagnosis, [2] deciding on testing strategies; [3] establishing pattern of inheritance; [4] identifying family members at risk; [5] calculating risk; [6] determining reproductive options
Often the most confusing aspect of pedigree interpretation
Non-paternity
Confounding factors in recognizing inheritance patterns [6]
[1] variable expressivity;
[2] clinical/genetic heterogeneity;
[3] sex influenced/limited gene expression;
[4] assortative mating (marrying the same looking person);
[5] small paternity size;
[6] lack of information
Usual patterns of inheritance [5]
[1] autosomal dominant; [2] autosomal recessive; [3] X linked recessive; [4] X linked dominant; [5] multifactorial
Unusual patterns of inheritance [3]
[1] mitochondrial DNA;
[2] triple repeat expansion;
[3] genomic imprinting
Affected genotypes of autosomal dominant inheritance
AA or Aa
Characteristics of autosomal dominant inheritance [3]
[1] no skipping of generations;
[2] both sexes affected in equal proportions;
[3] may be passed from male to male
If both parents are heterozygous for an autosomal dominant trait, what is the chance that the offspring will be severely affected?
25%
Achondroplasia - type of inheritance, site of mutation, characteristics
[1] autosomal dominant;
[2] FGF 3;
[3] short stature, skeletal dwarfism, midface hypoplasia, stenosis of spinal canal
Crouzon syndrome - type of inheritance, site of mutation, characteristics
[1] autosomal dominant,
[2] FGF 2,
[3] tower head skull (oxycephaly), supraorbital hypoplasia, eye proptosis/exopthalmos
Apert syndrome - type of inheritance, site of mutation, characteristics
[1] autosomal dominant;
[2] FGF;
[3] mental handicap, microcephaly, mitten hands
Marfan syndrome - type of inheritance, site of mutation, characteristics
[1] autosomal dominant;
[2] fibrillin 1 gene on chromosome 17;
[3] tall stature, scoliosis, arachnodactyly, positive thumb sign, positive wrist sign, dislocation of lens/myopia
Ehlers-Danlos syndrome - type of inheritance, nature of mutation, characteristics
[1] autosomal dominant;
[2] defect in collagen synthesis;
[3] cigarette-mark-like wounds on knees, stretchy skin
Affected genotypes of autosomal recessive inheritance
aa
Characteristics of autosomal recessive inheritance [3]
[1] both sexes affected in equal proportion;
[2] both parents must be carriers of a single copy of the gene for a child to he affected;
[3] risk is 25% per child of carrier parent
Harlequin syndrome - type of inheritance, site of mutation, characteristics, treatment
[1] autosomal recessive;
[2] keratin gene;
[3] ichthyosis, pseudo-amputation of digits, ectopion, eclabion;
[4] retinoin
Mucopolysaccharidosis 1 (MPS 1) - also called?; tyoe of inheritance, nature of mutation, characteristics, treatment
[1] Hurler’s syndrome;
[2] autosomal recessive;
[3] enzyme deficiency - lysozyme storage disease’
[4] regression of development/loss of developmental milestones, manifests at 2-5 years old;
[5] enzyme replacement treatment
Maple syrup urine disease - type of inheritance, nature of mutation, characteristics
[1] autosomal recessive;
[2] lack in enzyme for breakdown of branched amino acids (leucine, isoleucine, valine);
[3] branched chain amino aciduria, maple-smelling urine
Galactosemia - type of inheritance, nature of mutation, characteristics, therapy
[1] autosomal recessive;
[2] galactose-1-phosphate uridyltransferase deficiency;
[3] early cataracts, enlarged liver;
[4] soy-based milk formula, avoidance of foods with lactose
Characteristics of autosomal recessive inheritance [3]
[1] both sexes affected in equal proportion;
[2] both parents must be carriers of a single copy of the gene for a child to he affected;
[3] risk is 25% per child of carrier parent
For X linked inheritance, where is the gene locus found?
X chromosome
X linked recessive inheritance is more prevalent in which sex? why?
Males, because they only have 1 x chromosome
Harlequin syndrome - type of inheritance, site of mutation, characteristics, treatment
[1] autosomal recessive;
[2] keratin gene;
[3] ichthyosis, pseudo-amputation of digits, ectopion, eclabion;
[4] retinoin
[T/F] x linked recessive inheritance may be transmitted directly from father to son
F
x linked recessive inheritance - sons of carrier females will have ____ chance of being affected
50%
[T/F] all daughters of males affected with x-linked inheritance will be affected
T
[T/F] autosomal dominant traits may skip generations
F
Duchenne muscular dystrophy - type of inheritance, site of mutation, characteristics
[1] x linked recessive;
[2] 60% deletion of dystrophin gene;
[3] exaggerated lumbar lordosis, pseudo-hypertrophy of calf muscle, degeneration of muscles
MPS 2 - also called?, type of inheritance,nature of mutation, characteristics
[1] Hunter syndrome;
[2] x linked recessive,
[3] mucopolysaccharide storage disease –> enlarged spleen and liver, umbilical hernia, bone marrow invaded by mucopolysaccharides
Most common metabolic defect
G6PD deficiency
[T/F] x linked dominant inheritance - 50% of female children from affected mother will be affected
F - 100% will be affected
G6PD deficiency - type of inheritance, nature of mutation, characteristics
[1] x linked recessive,
[2] mutation in G6PD gene;
[3] no physical defects, no retardation, some medications/food may cause hemolytic anemia
[T/F] x linked dominant inheritance - no male children of affected father will be affected
T
Rett’s syndrome - type of inheritance, site of mutation, characteristics
[1] x linked dominant;
[2] MeCP2 gene –> methyl binding for regulation of other genes;
[3] affects females, lethal in males, microcephalis with growth; neurodevelopmental regression, characteristic hand movements
[T/F] multifactorial inheritance - most children with traits from this type of inheritance also have affected parents
F
[T/F] multifactorial inheritance - recurrence risk inreases with the number of affected children in the family. why?
T, because if many children have the trait, it probably means that the parents are carrying more copies of the genes needed for the trait to manifest
Leigh’s disease - type of inheritance, characteristics
[1] mitochondrial DNA inheritance;
[2] progressive loss of mental and movement abilities
[T/F] multifactorial inheritance - risk of affected relatives falls off very quickly with the degree of relationship
T
Spina bifida - type of inheritance, characteristics, treatment
[1] multifactorial inheritance;
[2] posterior meningocoele;
[3] immediate closure of the defect
Anencephaly - type of inheritance, characteristics, prevention
[1] multifactorial inheritance;
[2] skulless, brainless;
[3] folic acid at least 1 month before conception and during pregnancy
Oral clefts - type of inheritance, treatment
[1] multifactorial inheritance;
[2] surgical correction
Mitochondrial DNA is inherited from which parent? Why?
Mother, because these mitochondria are derived from the egg’s mitochondria
Heteroplasmy
Some mitochondria have mutated mtDNA, some do not
Mitochondrial DNA codes for: ____ [3]
[1] tRNA,
[2] rRNA;
[3] mitochondrial proteins
Homoplasmy
All mitochondria have either completely normal or completely mutated mtDNA
[T/F] mitochondrial DNA inheritance - a father may pass the trait on to his sons
F
Systems affected by mtDNA disorder
Any system that needs ATP/energy
Leigh’s disease - type of inheritance, characteristics
[1] mitochondrial DNA inheritance;
[2] progressive loss of mental and movement abilities
Kearns-Sayre syndrome - type of inheritance, characteristics
[1] mitochondrial DNA inheritance;
[2] opthalmoplegia, pigmentary retinopathy, ataxia
Myotonic dystrophy - mode of inheritance, nature of mutation, characteristics
[1] triple repeat expansion;
[2] CTG repeat;
[3] grip myotonia
Fragile X syndrome - mode of inheritance, nature of mutation, characteristics
[1] triple repeat expansion;
[2] CGG repeat in fragile site in long arm of X chromosome (FMR1 gene);
[3] mental retardation, speech delay, peculiar movement of arms, autism
Prader-Willi syndrome - mode of inheritance, nature of mutation, characteristics
[1] genomic imprinting;
[2] q11 to q13 region on paternal chromosome 15 is deleted/unexpressed;
[3] mild mental handicap, insatiable appetite, obesity
Angelman syndrome - mode of inheritance, nature of mutation, characteristics
[1] genomic imprinting;
[2] q11 to a13 region on maternal chromosome 15 is deleted/unexpressed;
[3] severe mental handicap, happy puppet syndrome
Principle of triple repeat expansion
Expansion of a segment of DNA that contains a repeat of 3 nucleotides –> high number of repeats causes disease
Phenomenon of Anticipation
In triple repeat expansion, repeats increase over successive generations and symptoms get worse and worse
Principle of genomic imprinting
We all inherit two copies of every autosomal gene (one from each parent). Both copies are functional for the majority of these genes; however, in a small subset one copy is turned off in a parent-of-origin dependent manner, causing abnormalities
Common manifestation of mitochondrial DNA abnormality
Energy-requiring processes of multiple organ systems affected
Examples of autosomal dominant disorders [5]
[1] achondroplasia [2] crouzon syndrome [3] marfan syndrome [4] ehlers-danlos syndrome [5] apert syndrome
Examples of autosomal recessive disorders [4]
[1] harlequin syndrome
[2] MPS1 / hurler’s syndrome
[3] maple syrup urine disease
[4] galactosemia
Examples of x linked recessive disorders [3]
[1] duchenne muscular dystrophy
[2] MPS2 / hunter’s syndrome
[3] G6PD deficiency
Examples of x linked dominant disorders [1]
[1] rett’s syndrome
Examples of multifactorial inheritance disorders [3]
[1] spina bifida
[2] anencephaly
[3] oral clefts
Examples of mitochondrial DNA inheritance disorders [4]
[1] leigh’s disease
[2] mitochondrial encelopathy, lactic acidosis, stroke-like episodes (MELAS)
[3] myoclonic epilepsy with ragged red fibers (MERRF)
[4] kearns-sayre syndrome
Examples of triple repeat expansion disorders [3]
[1] myotonic dystrophy
[2] fragile x syndrome
[3] huntington disease
Examples of genomic imprinting disorders [2]
[1] prader-willi syndrome
[2] angelman syndrome
