Genetics of De Novo Variants and Achondroplasia

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Questions and Answers

What does 'de novo' mean in the context of genetic variants?

Recessive in nature

Caused by environmental factors

Inherited from both parents

Newly occurring (correct)

How many mitotic divisions does a female germ cell undergo to form the zygote?

22 (correct)

Which gene variant is primarily responsible for Achondroplasia?

FGFR2

FGFR4

FGFR1

FGFR3 (correct)

What is the result of the G380R mutation in the FGFR3 gene?

Constitutive activation of FGFR3 Signup and view all the answers

Which characteristic is NOT associated with Achondroplasia?

Long extremities Signup and view all the answers

How many de novo variants do individuals typically have on average?

70 Signup and view all the answers

Which of the following is a consequence of Achondroplasia?

Increased risk of spinal pathologies Signup and view all the answers

What happens to bone growth due to the mutation in the FGFR3 gene linked to Achondroplasia?

There is excessive inhibition of bone growth Signup and view all the answers

What is the primary genetic cause of Achondroplasia?

FGFR3 G380R mutation Signup and view all the answers

How does the FGFR3 mutation affect bone growth?

It inhibits bone growth by making the protein constantly active Signup and view all the answers

Which of the following best defines an allele?

An alternative form of a gene that may result in different traits Signup and view all the answers

What is the effect of a missense mutation?

It results in a change of one amino acid to another Signup and view all the answers

What characterizes a nonsense mutation?

It converts a codon encoding an amino acid into a stop codon Signup and view all the answers

Which of the following describes a synonymous mutation?

A mutation that results in no change in the amino acid sequence Signup and view all the answers

What process is depicted by the central dogma?

DNA --> RNA --> Protein Signup and view all the answers

Which type of mutation is likely to have the most significant impact on protein function?

Nonsense mutation Signup and view all the answers

What characteristic describes most de novo variants according to the research?

They are primarily neutral. Signup and view all the answers

In human inheritance, how many de novo variants does each generation add to the previous generation's total?

70 Signup and view all the answers

What does the term 'polygenic' refer to?

A trait influenced by multiple alleles. Signup and view all the answers

What is highly unlikely regarding de novo variants under natural selection?

Few variants are subject to natural selection. Signup and view all the answers

What phenomenon is illustrated by the tree diagram in the context of human evolution?

A complex genealogy with accumulated variants. Signup and view all the answers

What happens to the accumulation of variants as generations pass?

Variants accumulate over time. Signup and view all the answers

Which of the following regions does the 'Out of Africa' model indicate humans migrated from?

Africa Signup and view all the answers

Which of the following statements accurately reflects the role of most genetic variants in humans?

Most variants have neutral or marginal impacts. Signup and view all the answers

What does the normal distribution curve of height indicate?

There is a spectrum of phenotype due to multiple genetic factors. Signup and view all the answers

Which is true about phenotypic variation in humans?

Most genetic variants are non-functional. Signup and view all the answers

What is an allele?

A specific form of a gene found at a specific location on a chromosome. Signup and view all the answers

Why does height in humans not fit Mendelian ratios?

Height is influenced by numerous alleles that interact with one another. Signup and view all the answers

What does the term 'de novo variants' refer to?

New genetic mutations that occur in an individual for the first time. Signup and view all the answers

Which statement best describes polygenic traits?

They contribute to a wide range of variation in a phenotype. Signup and view all the answers

How do genetic variants contribute to human traits?

Only a few variants significantly influence major traits. Signup and view all the answers

What is a key feature of polygenic inheritance?

Phenotype results from the interaction of multiple genes. Signup and view all the answers

Study Notes

De Novo Variants

De novo variants occur newly in the sperm from the father or the egg from the mother.
"De novo" means "newly occurring."
"Mutation" and "variant" have the same meaning, but "variants" is a more general term.
We all have some number of de novo variants, averaging around 70 variants.

Achondroplasia

Achondroplasia is the most common skeletal dysplasia found in humans.
It is caused by a variant in the FGFR3 gene.
FGFR3 plays a crucial role in regulating bone growth during development.
The G380R mutation is a specific point mutation within the FGFR3 gene.
The G380R mutation leads to a constitutively active FGFR3 receptor.
This constant activation disrupts the normal inhibitory function of FGFR3, leading to excessive inhibition of bone growth.

Variants/Mutations and Alleles

Variants are changes in DNA sequence.
Allele is “대립유전자” which is not the same as gene "유전자”.
Gene (유전자) encodes protein.
Allele is a change in DNA sequence.

Types of Variants

Synonymous/silent variant: No change in amino acid sequence.
Missense variant: Change in amino acid.
- Conservative missense: Change in amino acid with similar properties.
- Non-conservative missense: Change in amino acid with different properties.
Nonsense variant: Creates a stop codon, leading to a truncated protein.

Importance of De Novo Variants

Most variants are neutral and have no or very marginal impact on traits.
A few de novo variants are under natural selection.
A very few de novo variants are advantageous to selection.
Variants are neutral so can be segregated in current humans.

Polygenic Model

Polygenic refers to a trait or characteristic that is influenced by multiple alleles (variants).
It results in genetic diversity among individuals.

Genetic Diversity and Human Evolution

Human evolution is marked by a long and complex history.
Over millions of years, various factors have contributed to the accumulation of variants in the human genome.
As generations pass, variants accumulate in the genome.
Most variants are harmless, but some can lead to genetic diversity and adaptations.

Out of Africa

Humans migrated out of Africa, spreading across the globe over millions of years.

Phenotypic Variation

Phenotypic variation is sourced by de novo variants in every generation.
A few variants greatly contribute to traits and disorders, but most variants are neutral and are segregated to the next generation.

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Description

This quiz explores the mechanisms and implications of de novo variants, focusing on achondroplasia and the role of the FGFR3 gene. Understand how mutations impact skeletal development and the general significance of genetic variants. Test your knowledge on these vital concepts in genetics.