Human Genetics Flashcards
What percentage of humans are affected by Mendelian diseases at birth?
1%
Approximately 5% are affected at some point in their lives.
What is the percentage of pediatric hospital referrals that are for Mendelian diseases?
40%
This highlights the significance of Mendelian diseases in pediatric healthcare.
Why is identifying disease genes important?
- Genetic Testing for Disease Prevention (detects inherited diseases early)
- New Treatments (enables development of targeted therapies)
- Insight into Common Diseases (rare, inherited gene mutations help us understand more common diseases like Alzheimer’s)
What is an example of a genetic test for disease prevention?
Newborn blood spot tests
Tests for diseases like sickle cell, hypothyroidism, and cystic fibrosis.
What are two examples of drugs developed for Cystic Fibrosis?
- Orkambi
- Kaftrio
What does pedigree analysis investigate?
The occurrence of the disease in families to determine the type of disease mutation.
Looks at inheritance pattern
What is linkage analysis used for?
To look for evidence of genetic linkage between the disease gene and genetic markers.
Maps the disease gene as precisely as possible
What are the modes of Mendelian inheritance?
- Autosomal recessive
- Autosomal dominant
- X-linked recessive
- X-linked dominant
- Y-linked inheritance
- Maternal inheritance
What does incomplete penetrance mean?
Not all individuals with a mutation express the phenotype.
What is genetic heterogeneity?
Mutations in different genes can give the same disease.
What are short tandem repeats (STRs)?
Tandem repeats of a short sequence, usually 2-4 nucleotides, often in non-coding sequences.
What is the most common type of polymorphism in the human genome?
Single nucleotide polymorphisms (SNPs)
How can DNA profiling help law enforcement?
- Unique DNA profiles
- Crime scene evidence
- Database comparison
- Family links
What is positional cloning?
The process of identifying candidate genes by inspection of the human genome sequence in that region
Sequencing of the candidate genes in the affected and unaffected individuals = find mutation that causes disease
What is Next Generation Sequencing (NGS) used for?
To identify rare variants shared by only affected individuals.
It focuses on candidate genes for potentially causative variants and studies the functional impact of them
What was the goal of the 100,000 Genomes project?
To sequence 100,000 genomes to advance genetic research.
What can be inferred from a pedigree diagram?
The mode of inheritance of a mutation.
Fill in the blank: A _______ is a single nucleotide difference between individuals.
SNP
True or False: The chance of a random DNA match is less than 1 in a billion.
True
What is the typical distance between SNPs when using a GeneChip for genotyping?
One SNP per 3,000-6,000 bp
What does a pedigree diagram indicate if a trait skips generations?
It is likely caused by an autosomal recessive allele.
What is the inheritance pattern for X-linked dominant mutations?
Affected males pass the condition to all their daughters but to none of their sons.
What is a characteristic of autosomal dominant inheritance?
Phenotype appears in every generation and affects males and females equally.
What are the four types of Mendelian inheritance?
Autosomal recessive, Autosomal dominant, X-linked recessive, X-linked dominant
What characterizes Autosomal dominant inheritance?
Phenotype appears in every generation and affects males and females equally
Sometimes the homozygous mutant is lethal.
What is a key feature of Autosomal recessive inheritance?
Phenotype can skip generations
Both parents must be carriers to transmit the trait to the offspring
Affects males and females equally
What is the pattern of inheritance for X-linked dominant conditions?
Affected males pass on the condition to all their daughters but to none of their sons.
Affected heterozygous females with unaffected male partners pass on the condition to half their sons and daughters
How do affected heterozygous females transmit X-linked dominant conditions?
They pass the condition to half their sons and daughters.
What is the frequency of X-linked dominant mutations, such as Rett syndrome?
Occurs in 1/10,000 female births.
In X-linked recessive inheritance, how are sons and daughters affected when the mother is a carrier?
Half of sons predicted to be affected and half of daughters predicted to be carriers.
What is the outcome when a hemizygous affected male transmits an X-linked recessive condition?
None of his children are affected but all his daughters are carriers.
If an affected female has children in X-linked recessive inheritance, what will be the outcome?
All sons will be affected and all daughters will be carriers.
Fill in the blank: Autosomal dominant inheritance affects males and females _______.
equally
True or False: Autosomal recessive traits can appear in every generation.
False
What is a characteristic of Autosomal recessive traits regarding parents?
Both parents must be carriers to transmit the trait.
What is a Mendelian disease?
Caused by a single gene mutation
Why is pedigree analysis not simple?
- Incomplete penetrance = can have same mutation but different phenotypes
- Variable expressivity = expression may be low or high
- Delayed onset (e.g. Huntington’s disease)
- Genetic heterogeneity = different genes causing the same disease
- Non-paternity / misattributed paternity = not being sure of biological father
What DNA markers are commonly used for genetic mapping?
Short tandem repeats (STRs)
Single nucleotide polymorphisms (SNPs)
What must all DNA markers be?
Polymorphic = must be 2 or more alleles present in a significant proportion of the population
Easy to assay = must be easy to distinguish accurately one allele from another
How are SNPs used in linkage analysis?
- Crossing over occurs between the mutation and the SNPs (SNP1, SNP2, SNP3)
- SNP2 shows linkage with the disease in some pedigrees
- SNP1 shows linkage in all pedigrees
What are the key features of X-linked recessive inheritance?
- Transmission through unaffected carrier female = half of sons predicted to be affected and half the daughters predicted to be carriers (but none are affected)
- Transmission through hemizygous affected male = none of the children are affected but all his daughters are carriers
- Transmission through affected female = all sons will be affected and all daughters will be carriers
