Chapter I: Single Gene Disorders Flashcards
What are homologous chromosomes?
when 2 chromosomes contain the same genes, but because one is paternal and one is maternal may contain different alleles
Pseudoautosomal regions
The name for regions on X and Y chromosomes that are homologous
Gene.
sequence of DNA that encodes a specific protein (or non translated RNA; i.e tRNA, rRNA, or snRNA)
(basic unit of inheritance)
Locus.
physical location of a gene on a chromosome
Alleles
variation (mutation) in the DNA sequence of a gene produces a new allele at that locus. (different forms of a gene)
Many genes have multiple alleles
Polymorphism
when specific site on a chromosome has multiple alleles in the population
Atlhough the term alleles is used most frequently with genes, can noncoding DNA also be said to have alleles of specific sequences?
yes
The β-globin gene has been mapped to what location on a chromosome?
11p15.5 a specific location on chromosome 11
Is the β-globin gene polymorphic? Why?
yes because there have many mutations of it in the population and each mutation has created a new allele in the population
What is a genotype?
genetic makeup of organism
What are the types of single-gene mutations?
missense
nonsense
deletion
insertion
frameshift
Describe a missense mutation.
when there is a substitution of a single amino acid in the polypeptide chain
What is the missense mutation that leads to sickle cell?
caused by a missense mutation that produces a substitution
Valine replaces glutamic acid in the β-globin polypeptide
Describe nonsense mutations.
produce a stop codon resulting in a premature termination of translation and a truncated protein
Frameshift mutations?
When the inserted or deleted number of nucleotides is not a multiple of 3
In frame frameshift?
When the number of inserted or deleted bases is a multiple of 3
Can mutations occur in promoters and transcription factors?
yes
Loss of function mutations.
Mutations that cause a missing protein produce or cause decreased activity of the protein
What is recurrence risk?
the probability that the offspring of a couple will express a genetic disease
Label the pedigree nomenclature diagram.
Label the image
Meaning of proband.
the first affected individual to be identified in the family
Tricks for identifying if a pedigree is showing an AD condition.
- multiple generations of pedigree affected
- skipped generation not typically seen
- males and females affected equally
An example where two unaffected AD parents transmit disease causing allele.
if there was reduced penetrance
Most common type of parent genotypes that cause AD conditions?
Aa (heterozygous affected) individual with an aa (homozygous normal)
Recurrence rate for AD conditions.
50%
Be able to identify this pedigree.
Autosomal Dominant
What are important features that would help you distinguish AR inheritance
- typically seen in only one generation of a pedigree
- males and females affected equally
Most common genotype of parents producing a child with an AR condition.
two heterozygous (carrier) parents
Recurrence risk for offspring of the who have AR conditions?
25%
List some major AD diseases.
- familial hypercholesterolemia (LDL receptor deficiency)
- Huntington disease
- neurofibromatosis type 1
- Marfann syndrome
- acute intermittent porphyria
Consanguinuity.
the mating of related individuals
AR conditions.
- sickle cell anemia
- cystic fibrosis
- phenylketonuria (PKU)
- Tay-Sachs disease (hexominidase A deficiency)
What is the inheritance pattern show in this pedigree?
Autosomal recessive
What are some tricks to be able to ID X-linked recessive diseases?
- skipped generations are commonly seen
- male to male transmission not seen
Identify the inheritance pattern shown in this pedigree
X linked recessive inheritance
Name some X-linked recessive conditions.
- Duchenne muscular dystrophy
- Lesch Nyhan Syndrome (hypoxanthine-guanine phosphoribosyltransferase [HGPRT]
- Glucose - 6- phosphate dehydrogenase deficiency
- Hemophilia A and B
- red-green color blindness
- Menkes disease
- Ornithine transcarbomylase (OTC) deficiency
- SCID (IL-receptor y-chain deficiency)
Describe how offspring born to an affected male with a homozygous normal female presents if the condition is X-linked recessive?
all of the daughters will be heterozyogous carriers: all of the sons homozygous normal
What is the recurrence rate for a daughter with parents who have normal male with carrier female of an X linked recessive conditon?
recurrence rate for daughter is 0
What is the recurrence rate for a male born to a normal male and female who is a carrier of an X linked recessive condition?
The recurrence rate for a son is 50%
If the sex of a fetus born to a normal father and carrier mother is unknown, what is the recurrence rate in a fetus born to a normal male with a carrier female of an X-linked recessive condition?
Recurrence rate is multiplied by 1/2, the probability the the fetus is a male versus a female. Therefore if the sex is unknown, recurrence risk would be 25% overall
Why are women said to be mosaics with respect to the active X chromosome?
because they have paternal X chromosome active in 50% of cells and maternal X active in 50% of cells
X-chromsome inactivation is thought to be mediated by 1 mechinism or more than 1 mechinism?
more than 1
What are some ways the body causes X-chromosome inactivation?
- A gene called XIST has been identified as the primary gene that causes X inactivation. XIST produces an RNA product tha coats the chromosome, helping produces its inactivation
- condensation into heterochromatin
- Methylation of gene regions on the X chromosome
What exactly is genetic mosaiscism?
-the presence of 2 or more cell lines with different karyotypes in an individual.
-arises from mitotic nondisjunction
How may a female at times express an X-linked recessive mutation? What is the term for this?
Because of random inactivation of the X chromosomes carrying normal allele have been inactivated
manifesting heterozygotes
Why is the disease expression of a manifesting heterozygote typically milder?
because they have at least a small population of active X chromosomes carrying the normal allele
Which arm of the Y chromosome contains a large block of heterochromatin?
the q arm
Describe penetrance of males with Fragile X syndrome and symptoms?
Males: 100% penetrance
* intellectual disability
* large ears
* prominent jaw
* marcro-orchidism (usually postpubertal)
Describe the penetrance in females with Fragile X syndrome and the symptoms.
Females: 60% penetrance
intellectual disability
Is male to male transmission seen in X linked dominant conditions ?
no
Some tips to determine if the inheritance pattern is X-linked dominant in a pedigee?
examine children of an affected male none of the sons will be affected but all of his daughters will have the disease (assuming complete penetrance)
What is the inheritance pattern shown in this pedigree?
X-linked dominant inheritance
Explain how and individuals sons and daughters are affected if the male is affected and copulates with a homozygous normal female? (X linked dominant condition)
non of the sons affected: Recurrence rate 0%
all the daughters affected recurrence rate 100%
Recurrence rate if the sex of the fetus is unknown and there is an affected male with an X-linked dominant condition with a homozygous normal female?
then the recurrence rate is multiplied by 1/2 and overall recurrence rate is 50%
Recurrence rate if a normal male mates with a heterozygous affected female with an X-linked dominant conditin?
50% of sons affected
50% of daughters affected
