Affected most persons with the disease or trait are notated as?
Aa
Notation for Affected, rare and sometimes lethal?
AA
Unaffected “normal” persons are notated as?
aa
What is autosomal dominant inheritance?
When a disease or trait is caused by a dominant allele on an autosomal chromosome. Such mutations are expected to result in a phenotypic change
With a mating of Aa x aa what is the ratio of affected to normals?
50:50 or 1:1
broken down as Aa, Aa, aa, aa
With a mating of Aa x aa and the outcome being broken down as Aa, Aa, aa, aa. What are the odds of a 5th child being affected?
Each child is an independent event so the odds are 50:50
What is the most common genetic notation for someone with an autosomal dominant condition?
Heterozygous Aa
What are the 6 key features of someone with an autosomal dominance inheritance pattern?
1- an affected person has an infected parent
2- there is a ‘vertical’ look or pattern of affecteds seen in the pedigree
3-When and affected person mates with a normal, offspring are expected to be affected 50% of the time(and 50% are expected to be normal)
4- when the normal child of an affected person mates with a normal, normal offspring are expected
5- Sometimes an affected person does not have and affected parent, but there is a history of the condition in their family(this is a case of reduced penetrance)
6- Sometimes an affected person will appear in a pedigree with no prior history in that family( even though the condition is known to be dominant) this is a new mutation
What type of genetic disorder is Huntington’s Disease?
Autosomal dominant
Huntington’s disease:
Characterized by?
Mutation?
On set?
- progressive involuntary twitching, personality change and dementia, and death
- mutant gene has undergone a trinucleotide repeat or expansion mutation
- this is a age onset disease that usually sets in at around 40 yrs of age
What type of genetic disorder is Osteogenesis Imperfecta?
Autosomal dominant
Osteogenesis Imperfecta is a disorder of what?
Connective tissue disorder of type 1 collagen
OI is characterized by what?
brittle fragile bone disease and includes short stature, malformed bones, loose joints, blue sclera, opalescent teeth, and hearing deficit
There are many types of OI which one is the most common?
Type 1
Neurofibromatosis Type 1 is aka?
Von Recklinghausen Disease
What genetic mode of inheritance is Neurofibromatosis Type 1?
Autosomal dominant
What is Neurofibromatosis Type 1 characterized by?
Multiple neurofibromas
What is Achondroplasia aka?
Achondroplastic dwarfism
What mode of inheritance is Achondroplasia?
Autosomal dominant
What is Achondroplasia characterized by and what is the rate of new mutations?
1 non-proportional dwarfism
2 new mutations account for roughly 75% of all cases, possibly as high as 90%
What mode of inheritance is Marfan Syndrome?
Autosomal dominant
What is Marfan syndrome characterized by?
Tall persons with dis-proportionally long limbs, arachnodactyly, subluxation of the eye lens, and cardio vascular defects
Which mode of inheritance is Polycystic Kidney disease?
Autosomal dominant
What is Polycystic Kidney disease characterized by and what is the time of onset?
Multiple kidney cysts and ADPKD is later onset(young adulthood)
Define congenital
means present at birth and may be genetic
Define hereditary
means “to be inherited” and is genetic
Define Familial
means “runs in the families” and may or may not be genetic
Define genetic
means “caused be a gene(s)” and is a rather broad term
What is the most common blood coagulation disorder?
Von Willebrand’s disese
What causes autosomal recessive inheritance?
A disease or trait is caused by a recessive allele on an autosomal chromosome
When is a recessive allele not seen?
In the presence of a normal or dominant allele the mutation will not be seen in the phenotype
What are the 3 possible genotypes and the outcomes for recessive alleles?
AA=unaffected (most of the population)
Aa=unaffected (normal, but termed a carrier)
aa=affected (persons with the disease)
Looking at a recessive allele in the mating of Aa x Aa what would be the outcome ration of normal to affected?
3:1
What would the outcomes be for a recessive mating of AA x Aa?
1:1 but all would be “normal”
What are the 6 characteristics of autosomal recessive inheritance?
1 The vast majority of affected persons are the children of outwardly normal parents (and have no history in the families of the parents)
2 there is a “horizontal” look or patterns of affecteds in the pedigree
3 when the condition appears it has a recurrent risk of 25% in the sibship
4 When an affected mates with a normal, offspring are usually normal
5 When an affected mates with an affected, affected offspring are expected
6 if the abnormality is rare, one often finds consanguinity in the pedigree
Does a normal person carry harmful recessive alleles?
Yes, harmful recessive alleles are relatively common in the human population and are usually referred to as part of the genetic load or burden
With the mating of a Pp x Pp what is the chance of getting a carrier? This only applies to recessive alleles
PP, Pp, Pp, pp- (no pp because affected) so of PP, Pp, Pp only Pp will be a carrier leaving 2 out of 3 chance of being a carrier aka 2/3
What mode of inheritance is PKU?
Autosomal recessive
What is PKU a disorder of?
amino acid metabolism
What does PKU result in and what are the clinical features of this?
Accumulation of phenylaline which leads to severe mental retardation, hypo-pigmentation, and an unusual odor
How common is PKU?
uncommon(1 in 15,000)
Albanism is aka?
hypomaelanism
What is the mode of inheritance for Albanism?
autosomal recessive
What is Albanism a disorder of?
amino acid metabolism
What does Albinism result in and is it common?
results in a deficiency of melanin and is uncommon
What is Tay-Sachs disease aka?
GM2 gangliosidosis
What is the mode of inheritance for Tay-Sachs disease?
Autosomal recessive
What is Tay-Sachs disease a disorder of?
Lipid metabolism
Is Tay-Sachs disease common?
It is uncommon to rare, but variable depending on the population as in the case with the Ashkenazi Jews
What is cystic fibrosis also known as?
CF or mucoviscidosis
What is the mode of inheritance for cystic fibrosis?
Autosomal recessive
What is cystic fibrosis a disorder of?
Chloride transport
Cystic fibrosis results in exocrine gland secretion difficulties whcih lead to what?
very salty sweat, thick respiratory mucus secretions(leads to bacterial growth and respiratory infects), blockage of billiary tract(poor digestion), and pancreatic insufficiency
What is the population prevalence of cystic fibrosis?
not common
co-dominant or intermediate inheritance can be described as?
Heterozygotes have a different phenotype than either of the homozygous types(although often only a slight difference)
What are the three possible genotype outcomes for co-dominance?
AA= unaffected Aa= semi-affected aa= affected
What is familial hypercholesterolemia aka?
Hyperlipoproteiemia type IIa
What mode of inheritance is familial hypercholesterolemia?
autosomal co-dominant
What is familial hypercholesterolemia a disorder of?
High serum cholesterol specifically LDL’s due to an LDL receptor issue
In familial hypercholesterolemia as a result of co-dominance there is a form of the disease for the heterozygous carrier and a very severe form of the disease when homozygous. What is the prevalence, cholesterol levels, and risk of MI for the mild form?
Mild form possibily as common as 1 in 500-the heterozygotes.
Total serum cholesterol in the 250-500mg/dl range
risk of MI is elevated: by age 60, seen in 85% of males and 50% of females
Severe form just know that is is very rare (serum cholesterol is 500-1000 and MI by age 20)
What mode of inheritance is sickle cell anemia?
An autosomal co-dominant disorder
What does sickle cell anemia cause?
vasculature gets occluded causing a vaso-occlusive crises and RBCs are rapidly destroyed causing anemia
What are heterozygotes with sickle cell anemia like?
they are essentially normal, but RBCs will sickle in a low oxygen environment and they have what is called the sickle cell trait
How predominant is sickle cell anemia?
African and/or mediterranean descent people
Also 1 in 12 african americans has the sickle cell trait
What is the advantage to having the sickle cell trait?
Carriers of this mutation are somewhat resistant to the malaria infection
What are 3 more examples of co-dominance?
beta-thalassemia, Factor V- Leiden Thrombolphilia, and ABO blood types
What do Beta-Thalassemia heterozygotes and homozygotes have?
Heterozygotes have mild microcytic anemia (thalassemia minor)
Homozygous recessives have severe anemia (thalassemia major)
What does Leiden Thrombophilia cause?
Common cause of venous embolism
one copy of the gene increases the chance of thromboembolism
What is an example of perfect co-dominance?
ABO blood types
What is SRY?
Sex determining Y region
Where is the vast bulk of genes for determining sexual differences?
on the autosomes
Heterogametic sex are male or females?
Males
Homogametic sex are males or females?
Females
What is a Barr body?
An X chromosome that is shut down
What is klinefelter’s syndrome aka?
Testicular hyalinization
What is the karyotype for klinefelters syndrome?
47, XXY
Which gender is affected by klinefelters?
Males
What are the characteristic features of klinefelters?
Sterility, tall/lanky, gynecomastia and the condition is uncommon
What is turner’s syndrome also known as?
gonadal dysgenesis
What is the karyotype for turners syndrome?
45, XO
Which gender is affected by Turner’s syndrome?
females
What are the clinical features of turners syndrome?
Sterility, broad”shield” chest, “webbed” neck,
How common is Turner’s syndrome?
somewhat uncommon, also about 10% of all spontaneuos abortions
Which people are more often described as “intersex”?
hermaphroditism
Are sex chromosome abnormalities common?
yes
What are genes on the Y chromosome known as? SRY for example?
holandric genes
What is the only type of x linked inheritance that we are learning about?
X-linked recessive
Since males only have 1 x linked chromosome what would that be called?
Hemizygous
With the mating of a male and a female carrier what would be the outcome? Aa, AY
AA, Aa, AY, aY This would give a ration of 3:1 affected. Only a male would be affected
What are the 2 characteristics of X-linked recessive inheritance?
1 The vast majority of affected persons are males
2 An affected male cannot pass the trait on to his son or to further generations though his son
What genetic mode of inheritance is Hemophilia A?
X-linked recessive
What is Hemophilia A due to?
Missing the blood clotting factor VII
How common is Hemophila A and what does it result in?
It is very uncommon and results in bleeding
Which gender is affected by Hemophilia A?
Only males
What is the genetic mode of inheritance for common color blindness?
X-linked recessive
How common is common color blindness and what does it cause?
It is very common(1 in 12 males) and results in red-green confusion
WWhat mode of inheritance is Duchenne-Type Muscular Dystrophy?
X-linked recessive
What mode of inheritance is fragile-X syndrome?
X-linked recessive
What does fragile x cause in a person?
mental retardation
What is the most common cause of mental impairment?
fragile x syndrome
What mode of inheritance is male pattern baldness?
x-linked recessive
male pattern baldness is aka?
androgenic alopecia
What is up with male pattern baldness?
It is a pattern of hair loss in males due to the presence of androgen hormones
Is male pattern baldness common?
Yes very common
