Term
| Glossary: 1)Gene 2)Alleles 3)Homologous chromosomes 4)heterozygous 5)homozygous 6)hemizygous 7)dominant 8)recessive 9)genotype 10)phenotype 11)mutation |
|
Definition
1) specific segment of DNA on a chromosome which contains information for production of a functional product
2) alternative forms of a gene occupying the same locus on homologous chromosomes
3) two members of a pair of chromosomes
4) different alleles at each of the two homologous loci
5) both alleles are the same
6) A male is hemizygous for alleles on the X chromosome
7) when the condition is manifest in heterozygotes
8) when manifest only in homozygotes
9) the genetic constitution of an individual, either overall or at a specific locus
10) the observed characteristics of an individual, produced by the interaction of genes and environment/other genes
11) alteration in DNA sequence |
|
|
Term
|
Definition
multiple effects of a single gene
-Ex: For Duchenne Muscular dystrophy, the muscles are affected, but there are also intellectual effects |
|
|
Term
|
Definition
1) similar phenotypes due to different genetic abnormalities
-Ex: There are many types of muscular dystrophy that all result in muscle weakness but there can be many different genes responsible. |
|
|
Term
|
Definition
1) Count up males and females- in autosomal dominant diseases, there are an even number M/F affected
2) Successive generations affected
3) One-half of offspring at risk are affected
4) Male to Male Transmission- if you have this then you can see that it’s not X linked (except in the case of XXY- Klinefelter syndrome)
5) If both parents are heterozygous for an autosomal dominant allele, there is a ¾ chance that offspring will be affected. (Sometimes inheriting the homozygous form of a disease in this situation will result in death or inability to reproduce.)
6) Ex AD disease: male pattern baldness but it’s expressed in males, not females |
|
|
Term
|
Definition
1) Incidence is 1 in 4000
2) autosomal dominant
3) variable expressivity- ie. What features the patient shows; the way a patient manifests sypmtoms as opposed to complete penetrance.
4) complete penetrance- whether a symptom is present or not (all or none)
5) high mutation rate- 50%
6) neurofibromin gene-17q11.2 350kb
7) tumor supressor gene
8) DNA mutation detection rate 95%
(don’t need to know all characteristics but things like “autosomal dominant” ARE important) |
|
|
Term
| Diagnosis of NF1- at least 2 required |
|
Definition
• Café au lait spots
• Axillary, inguinal freckling- skin abnormalities
• Neurofibromas- cutaneous, plexiform- tumors (either surface or deeper tissue)
• Lisch nodules- one of hallmarks
• Optic glioma
• Tibial pseudoarthrosis, sphenoid dysplasia- bowing of tibia/ skeletal abnormalities
• Parent, sibling or child with NF1
• Could have short stature or large head
-Commonly mother or father is also diagnosed when a child is diagnosed (They could be carriers even if they aren’t expressing an allele) |
|
|
Term
|
Definition
The extent to which the genetic defect is expressed
Variable expressivity – expression of the trait may vary from mild to severe; few vs. many manifestations |
|
|
Term
|
Definition
Refers to all-or-none expression of a trait
• May appear as a skipped generation
• May be age or sex dependent
• Reduced penetrance – condition is expressed in less than 100% of persons who carry the gene
Misc. Fact: In Huntington’s disease you have age dependent penetrance. |
|
|
Term
|
Definition
• Most common form of adult muscular dystrophy
• Myotonia, muscle weakness and wasting, facial diplegia- looks dull/expressionless
• Cardiac conduction defects
• Cataracts, diabetes, hypogonadism
• Congenital form – more severe effect in offspring of affected mothers as oppsed to father’s
• CTG trinucleotide repeat – unstable (like fragile X is unstable)
• Sustained grasping: A quick check is a hand shake- they won’t be able to release easily so frequently they give limp handshake to avoid embarrassment. If this happens, have them grasp your thumbs and then let go. (it takes a long time to let go.) |
|
|
Term
| AUTOSOMAL DOMINANT CONDITIONS |
|
Definition
• incomplete penetrance (can result in skipped generations)
• variable expressivity
• higher rate of new mutations, particularly in conditions with reduced reproductive fitness
Ex: A baby with achondroplasia (AD) will have excess skin folds. This is shown to show us that there is a high mutation rate in autosomal dominant conditions. About 80% are from new mutations, partially because there is social selection against people with AD diseases. Rate increases with increased age of father. Achondroplasia is 100% penetrant. If two normal parents have a baby with achondroplasia, they do have a slightly increased chance of having another baby with the disease. This is due to mosiacism (either in general body cells or just in gonads). The child affected will then have a 50% chance of having a baby with achondroplasia with another normal parents. |
|
|
Term
|
Definition
• Males and Females affected equally
• Single generation affected
• One-fourth offspring at risk are affected
• Parents can be blood relatives (helpful clue but they usu. aren’t)
• Only expressed when both genes are abnormal. People usually carry 8-10 recessive genes for random conditions.
• If your’e a nonaffected carrier of an AR disease with a normal parent, there’s a 50% chance of having a child, who is a carrier
• If you’re affected and your spouse is noncarrier, all children will be carriers but not affected.
• With something more common like sickle cell disease in the African American population, a carrier with a heterozygous mate, it’s 50:50 that they’ll have affected offspring
Ex: Cystic fibrosis
If you are normal but have a child with CF, you have a chance of 100% of being a carrier. The chance of parents having another child with CF is 50%. 2/3 of healthy kids wil be carriers.
Ex: Hurler’s syndrome (a storage disease):
Symptoms: hypotonia, large head, protuberant abdomen, slow growth, short neck, respiratory problems, cataracts, corneal clouding (pleiotropic effects)
-a mucopolysacharide disorder |
|
|
Term
|
Definition
• Males only affected
• Sporadic generations affected
• One-half sons at risk are affected
• Daughters of affected males are carriers
• If woman is carrier, see 50% of sons with the disease and 50% of daughters are carriers. There is not male-to-male transmission
• If female is homozygous, then 100% of sons will be affected, 50% of daughters
Ex: For hemophilia, there is reduced reproductive fitness so usually can’t reproduce.
Ex: Another mucopolysaccharide disorder: No neck, protuberant abdomen, can’t stretch out fingers. |
|
|
Term
| DUCHENNE MUSCULAR DYSTROPHY |
|
Definition
• incidence is 1 in 3300 males
• most common severe muscular dystrophy
• X-linked recessive
• dystrophin gene- Xp21.2 2400kb (large gene)
• 1/3 are new mutations
• 65% are deletions-frameshift mutations
Symptoms- psuedohypertrophy of calves in seen in children |
|
|
Term
|
Definition
| random inactivation of one X chromosome in the somatic cells of females in early embryonic life. This leads to mosaicism for X-linked disorders and explains variable expression in female heterozygotes |
|
|
Term
|
Definition
• Most common inherited form of mental retardation in males
• Incidence 1/3000 males
• Locus at Xq27.3
• Increase in CGG repeats with inactive methylation status
• X-linked semi-dominant**- because women who are carriers can be clinically affected
• Carrier females may be clinically affected**
• Transmitting males may be clinically unaffected ** (because it’s a pre-mutation) |
|
|
Term
|
Definition
• Retardation - mild to severe
• Macro-orchidism
• Elongated face, prominent jaw
• Prominent ears
• Connective tissue dysfunction
• Hyperactivity, autistic features, speech difficulties |
|
|
Term
|
Definition
• Females affected more often than males
• Successive Generations Affected
• ½ children of affected female affected
• All daughters, no sons of affected male are affected
• No male to male transmission
Ex: Rett syndrome is X linked dominant and lethal in hemizygous affected males (miscarried or spontaneously aborted) |
|
|
Term
|
Definition
| expressed in both sexes but with different frequencies. (ex: male pattern baldness- AD but expressed more (only) in males; Hemochromatosis- AR, expressed more severely in males because females have their own way of getting rid of extra blood through menstruation) |
|
|
Term
|
Definition
| • Males passed to all male children |
|
|
Term
|
Definition
• 16,568 bp ds circular DNA
• 13 polypeptides that are subunits of enzymes of oxidative phosphorylation
• 22 transfer RNAs
• 2 ribosomal RNAs
• hundreds of copies per cell
• These are very complex and confusing. Mito have their own genome. Most of thse genes code for processes involving oxidative phosphorylation. So organs that depend more heavily on oxidative phosphorylation for energy (brain, eye, etc) are more heavily affected.
• See disorder only passed by females but males and females are equally affected
• Dominant pattern of transmission because affected mother has affected children
• No male to male transmission |
|
|
Term
| MITOCHONDRIAL INHERITANCE |
|
Definition
• vertical transmission by females only
• proportion of affected offspring may exceed 50%
• cells may contain a mixture of normal and abnormal mtDNAs
• mitochondria are randomly transmitted to daughter cells during cytokinesis
• phenotypic expression is variable depending on the proportion of abnormal mtDNAs |
|
|
Term
|
Definition
• MELAS-Mitochondrial Encephalomypathy, Lactic Acidosis, Stroke-like episodes
• MERRF-Myoclonus Epilepsy with Ragged Red Fibers
• Kearns-Sayre syndrome
• ophthalmoplegia
• retinal degeneration
• heart block
• Leber's hereditary optic atrophy
• blindness in early adulthood |
|
|
Term
|
Definition
• Determination of the inheritance pattern in a family permits assessment of risk of the disorder to other family members.
• Reduced penetrance, variable expressivity and new mutations are characteristics of autosomal dominant conditions.
• Mitochondrial disorders show vertical transmission, variable phenotype and are transmitted only by females. |
|
|
Term
1) DUCHENNE MUSCULAR DYSTROPHY
2) Fragile X syndrome
3) Cystic fibrosis
4) Hurler's Disease
5) Achondroplasia
6) MYOTONIC DYSTROPHY
7) NEUROFIBROMATOSIS
8) MELAS-Mitochondrial Encephalomypathy, Lactic Acidosis, Stroke-like episodes
9) MERRF-Myoclonus Epilepsy with Ragged Red Fibers
10) Kearns-Sayre syndrome
11) Leber's hereditary optic atrophy
blindness in early adulthood |
|
Definition
1)X-recessive. psuedohypertrophy of calves in children.
2)X-semi-dominant-mutation. Affects carrier females but not necessarily male transmitters since it is a pre-mutation. Mental Retardation, big ears.
3) AR.
4) AR. large head, mucopolysacharide problem.
5) AD. Lots of mutations.
6) AD. • Myotonia, muscle weakness and wasting, facial diplegia- looks dull/expressionless. Sustained grasping.
7) AD. Complete penetrance, variable expressitivity. Lisch nodules- one of hallmarks; Optic glioma; Tibial pseudoarthrosis, sphenoid dysplasia; bowing of tibia/ skeletal abnormalities
8-11) MD
10) ophthalmoplegia
retinal degeneration
heart block |
|
|
Term
|
Definition
Reduced penetrance, variable expressivity and new mutations are characteristics of ______________ conditions.
_____________ disorders show vertical transmission, variable phenotype and are transmitted only by females.
Answer:
autosomal dominant;
Mitochondrial |
|
|
Term
Different Modes of Transmission
i. Autosomal Dominant
ii. Autosomal Recessive
iii. X-linked dominant
iv. X-linked recessive
v. Y-linked
vi. Mitochondrial |
|
Definition
i.
1. Passed on from mom and dad to offspring: successive generations affected
2. Male to male transmission: shows that it cannot be X-linked
3. ½ offspring are at risk are affected
ii.
1. Single generations affected
2. Both male and females affected
3. ¼ of offspring effected (if both heterozygote’s)
iii.
1. More females than males affected since females have 2 chances of getting it
2. Seen in successive generations
3. Affected female has 50% chance of passing on and affecting progeny
4. Affected males will always pass onto girls not boys
iv.
1. Seen in sporadic generations
2. Mostly males get it, since females are usually carriers
3. Affected males --> female carriers
4. No male – male transmission
5. Males only affected
6. ½ sons at risk are affected
7. Daughters of affected males are carriers
v.
1. all males in ever generation get it, different from X-linked recessive because you don’t see it in every generation
vi.
1.transmitted by mothers, more than 50% of offspring affected, only vertical transmission by females only
2. Both males and females affected, but only females can pass it on |
|
|
