1
Q
-
-
A
- Craniofacial anomalies tend to recur in families.
- Risk for recurrence is variable.
- It depends on interactions of environmental and genetic factors.
2
Q
Deoxyribonucleic Acid (DNA) -Located in
A
- Located in the nucleus of the cell
- Consists of nucleotides which contain:
–A5-carbon sugar (deoxyribose) chemically bonded to:
—Nitrogenous base
- ——-Purines—adenine (A) and guanine (G)
- ——-Pyrimidines—thymine (T) and cytosine (C)
—Phosphate group—links the nucleotides together at the 5th and 3rd carbons of the sugar
3
Q
Deoxyribonucleic Acid (DNA) - DNA forms..
A
- DNA forms long polymers (macromolecules) composed of repeating structural units.
- Two strands coil together to form a double helix.
- –Purine is always paired with a specific pyrimidine in the opposite strand (e.g., A-T and C-G pairs).
4
Q
Replication
- definition
- process
A
- Replication is the process of making two identical DNA molecules from one.
- One strand of the double helix allows DNA to serve as a template for its own replication.
- Process:
- -Double helix is unwound.
- -Complementary strands are separated.
- -Nucleotides are added to each single strand sequentially, forming new complementary strands.
- -The result is two identical double helix molecules of DNA.
5
Q
Genes and Chromosomes
-defintions
A
Gene—submicroscopic functional unit of heredity, consisting of a discrete segment of a DNA strand within a chromosome
Chromosome—a single, linear double strand of DNA with associated proteins
6
Q
Genes
-consist of?
A
- Thousands are found in each chromosome.
- Genes consist of the following:
- -A promoter region—starting point for the gene’s activity and serves as an on/off switch
- -A coding region—contains information needed to make a functional protein
- -Regulatory elements—determine how much of the protein will be made
7
Q
Genes
changes and mutations
A
- Changes in the coding region of a gene may lead to mutations (deletions or insertions) that disrupt gene function.
- Mutations can result in various diseases or malformations.
- Polymorphism—variability in genes among individuals
- -Polymorphism is common in virtually all genes.
- -It contributes to the uniqueness of each individual.
- -New variants that improve function may become more common over time.
- -New variants that lead to disease will remain rare or be eliminated.
8
Q
Ribonucleic Acid (RNA)
- general info
- transcription
A
-Similar to DNA, but
- -Are located in the cytoplasm, not the nucleus
- -Is a single strand rather than a double strand
- -Has ribose as the sugar rather than dextrose
- -Has the pyrimidine uracil (U) in place of thymine (T)
-Transcription—a process in which a complementary strand of DNA is created with a single-strand template
9
Q
RNA
Amino acids—
Polypeptide—
Protein—
A
Amino acids—the building blocks of proteins
Polypeptide—a sequence of amino acids
Protein—consists of polypeptides
10
Q
RNA
determines.. coding region (\_\_\_ and \_\_\_)
A
- RNA determines which amino acids will be incorporated into the protein.
- Coding region—determines the amino acid sequence for a polypeptide
- -Exons—segments of the coding region that are spliced together to form a continuous RNA coding sequence
- -Introns—segments between exons that are spliced out follow
11
Q
Messenger RNA or mRNA
general info
ribosomes?
A
- RNA that has had the introns removed
- Is transported from the nucleus to the cytoplasm to function as a template for protein synthesis
- Ribosomes—organelles that attach to mRNA and translate nucleotides into the specified polypeptide (amino acid sequence), forming a template for protein synthesis
12
Q
Chromosomes
A
- Linear double strands of DNA with associated proteins
- Function to organize and compact the DNA in a cell
13
Q
Chromosomes
- genome
- karotype
A
Genome—a complete set of instructions for a particular organism or species
Karotype—a visual profile of an individual’s chromosomes
14
Q
Chromosomes
- centromere
- types of chromosomes
A
- Centromere—narrowed region of each chromosome that is important for cell division
- Types of chromosomes:
- -Metacentric chromosomes—contain a centrally located centromere
- -Submetacentric chromosomes—centromere is off center, leading to a short “p” arm and a long “q” arm
- -Acrocentric chromosomes—centromere is close to one end of the chromosome
15
Q
Chromosomes
Each contains..
A
- Each chromosome contains:
- -A centromere—narrowed region that is important for cell division
- A chromosome may contain:
- -A “p” arm—short arm on each side
- -A “q” arm—long arm on each side
16
Q
chromosomes
how many?
females vs. males
A
- Each pair of chromosomes is numbered from 1 to 23.
- Chromosomes from 1 to 22, called autosomes, are numbered according to length (longest is 1 and shortest is 22).
- The 23rd pair, called the sex chromosomes (X and Y), determine gender.
- -Females have two X chromosomes (one from each parent), written as 46, XX.
- -Males have an X (from the mother) and a Y (from the father), written as 46, XY.
17
Q
chromosomes
ideogram?
A
- Chromosomes can be stained to reveal light and dark colored bands.
- Ideogram—a schematic drawing of the banding pattern of a chromosome
18
Q
chromosomes
specific genes are labeled by..
used to describe the..
A
-Specific genes are labeled by the chromosome number, arm (“p” or “q”) and band number to indicate its location relative to the centromere and the other bands on that arm.
- Chromosomes are used to describe the rough location of genes in gene mapping studies.
- -Example: lp36 means the gene is on the short arm of chromosome 1 in the band labeled 36
19
Q
cell cycle
A
- Cells alternate between states of active division and nondivision.
- Cell cycle—the process of preparing for and undergoing cell division
- Frequency depends on the type of cell and the rate of growth of the organism at the time.
- Steps are similar for all types of somatic cells (all cells except, those for reproduction).
20
Q
Cell cycle
- mitosis
- cytokinesis
A
-Two major processes:
- -Mitosis—process of separating duplicated chromosomes and reconstitution of two cell nuclei
- —Takes place in the somatic cells
- —An identical set of chromosomes is distributed to each daughter cell
- —Results in daughter cells that have the same number of chromosomes (46) as the parent cell
–Cytokinesis—the separation of the cell cytoplasm to form two distinct cells with separate cell membranes
21
Q
Cell cycle
meiosis
interphase
A
- Meiosis:
- -Meiosis ccurs only in the production of gametes, which are sperm from the testes and ova (eggs) from the ovaries.
- -Process results in 23 chromosomes rather than 46.
- -When sperm and ova combine to form a zygote, the organisim will have 46 chromosomes.
- -Cells division results in cells that each have a single copy of each chromosome.
-Interphase—the time between cell division
22
Q
Chromosomal Abnormalities
nondisjunction
monosomy
A
- Nondisjunction—failure of chromosome to separate during cell division
- Monosomy:
- –Loss of one copy of a chromosome results in only a single copy of a chromosome.
- –Monosomy X results in Turner syndrome.
23
Q
Chromosomal Abnormalities
trisomy
A
Trisomy:
- Trisomy is caused by gaining one extra copy of a chromosome, for a total of three chromosomes
- Trisomy can occur for 13, 18, 21 (Down syndrome), or X.
24
Q
Chromosome Abnormalities
mosaicism
deletions
A
- Mosaicism—when the cells have different genetic contents in a single individual
- Deletions—when part of a chromosome becomes separated and lost
25
-chromosome abnormalities
duplications
translocation
inversions
- Duplications—when a part of a chromosome is duplicated
- Translocations—when there is a transfer of genetic material between two or more chromosomes
- Inversions—when a portion of a chromosome is turned 180° from its usual orientation
- -Note: Small mutations involving single genes are more common than chromosomal abnormalities.
26
chromosome abnormalities
normal and deleted..
associated with..
Normal and deleted human chromosome 4 with ideograms
| Associated with Wolf-Hirschhorn syndrome
27
Chromosomal Analysis
chromosomes are..
for those too small to be seen...
-Chromosomes are condensed during certain stages of the cell cycle, to be easily viewed under a microscope.
- For abnormalities that are too small to be seen with routine analysis, a special technique called fluorescence in situ hybridization (FISH) is used in a cytogenetics lab.
- -FISH is needed to identify deletions on chromosome 22qll.2, associated with velocardiofacial syndrome
28
chromosomal analysis
cytogenetics
contiguous gene syndromes
- Cytogenetics (cell genetics)—a branch of genetics dealing with the structure and function of the cell, particularly the chromosomes
- Contiguous gene syndromes—caused by deletions that contain several genes
29
mendelian ingeritance
definition?
patterns include?
allele is?
-Mendelian inheritance—patterns of inheritance first described by Mendel in his studies on peas in 1866
- Patterns include:
- -Autosomal recessive
- -Autosomal dominant
- -X-linked patterns
-Allele—a copy of a gene
30
mendelian inheritance
pattern depends in __ and ___
- Pattern of inheritance of a trait depends on whether the individual is:
- -Homozygous—has the same allele of the gene for a trait
- -Heterozygous—has two different alleles of the gene for a trait
31
pedigree
definition?
Pedigree—a pictorial representation of family members and their line of descent
32
Autosomal Recessive Inheritance
definition?
- Autosomal recessive—a trait that manifests only when mutations are present in both copies of a gene
- Only homozygous individuals will have features typical of the phenotype of an autosomal recessive condition.
33
Autosomal Recessive Inheritance
-When two heterozygous carriers of an autosomal recessive condition mate:
- -There is a 25% risk that the child will receive a copy of the abnormal gene from each parent and become affected.
- -There is a 50% risk that the child will receive a single copy of the abnormal gene from one parent and become a carrier.
34
Autosomal Recessive Inheritance
- consanguinity
- hetergeneity
- Consanguinity—mating between related individuals
- -Leads to increased risk that the both members of the couple carry the same disease-causing mutations of the same genes
-Heterogeneity—a condition where a specific phenotype can be caused by mutations of different genes
35
Autosomal Dominant Inheritance
definition
- Autosomal dominant—a trait that manifests when mutations are present in only one copy of a gene
- Both homozygous and heterozygous individuals will have features typical of the phenotype of an autosomal dominant condition.
36
Autosomal Dominant Inheritance
- When two individuals with a dominant condition mate:
- When one individual with a dominant condition and an unaffected partner mate:
- When two individuals with the same autosomal dominant disorder mate:
- When two individuals with a dominant condition mate:
- -There is a 100 % chance that they will pass the condition to their offspring, who will be homozygotes with two copies of the defective gene.
- When one individual with a dominant condition and an unaffected partner mate:
- -There is a 50% risk with each pregnancy of passing the condition to their offspring (who will be heterozygotes).
- When two individuals with the same autosomal dominant disorder mate:
- -There may be unaffected children if both parents are heterozygotes, with one normal and one abnormal allele.
37
Autosomal Dominant Inheritance
incomplete penetrance
pleiotropy
- Incomplete penetrance—the lack of a recognizable phenotype in an individual who carries a gene for an autosomal dominant trait or condition
- Pleiotropy—where a single mutant gene can affect multiple, unrelated systems (e.g., heart, skin, bones, etc.)
38
X-linked inheritance
caused by..
affects..
- X-linked inheritance—caused by genes on the X chromosome
| - Affects mostly males because they inherit only one allele of the X chromosome, whereas females inherit two copies
39
x-linked inheritance
x-linked recessive conditions.. (6)
-X-linked recessive conditions:
- -These affect males almost exclusively
- -Females have only a mild effect or no effect.
- -Carrier females transmit the defective genes to 50% of their sons, who will be affected.
- -Carrier females transmit the defective genes to 50% of their daughters, who will be carriers.
- -Affected males pass the gene to 100% of their daughters
- -There is no father-to-son transmission because fathers do not give an X chromosome to their sons.
40
x-linked inheritance
affected males:
affected females:
- X-linked dominant conditions: rare, with only a few known disorders
- -Affected males:
- ---Transmit the disorder to all daughters
- ---Do not transmit to sons, because they receive the Y chromosome from the father
- ---Many X-linked dominant disorders that are lethal to males
- -Affected females:
- ---Are more often affected than males
- ---Can transmit the disorder to offspring of both sexes
41
Non-Mendelian Inheritance
-Inheritance that does not follow the basic rules of Mendelian inheritance includes:
- Inheritance that does not follow the basic rules of Mendelian inheritance includes:
- --Multifactorial inheritance
- --Anticipation
- --Imprinting
42
Multifactorial Inheritance
definition?
teratogens?
- Multifactorial inheritance—when disorders result from an interaction of multiple genes with environmental influences
- Teratogens—environmental factors known to increase risks for birth defects
43
Multifactorial Inheritance
2 categories?
-Two categories of multifactoral inheritance abnormalities:
1. Continuous variation abnormalities
- --These include traits on a continuum, such as height, weight, intelligence, and blood pressure.
- --Border between normal and abnormal is subjective and a matter of arbitrary definition.
2. Threshold abnormalities
- --These include cleft lip/palate, pyloric stenosis, and neural tube defects.
- --Trait is either present or absent.
- --As the number of risk factors increases, the additive risk may cross a threshold, resulting in expression of the trait.
44
Multifactorial Inheritance
- Recurrence risk
- -Increased with greater severity
- -Increased in close relatives because:
- ---They share genetic backgrounds.
- ---They have similar environmental risk factors.
45
Anticipation
-definition?
Anticipation—a tendency in certain inherited disorders to have more severe manifestations or an earlier age of onset with succeeding generations
46
Imprinting
definition?
if maternally imprinted..
if paternally imprinted..
- Imprinting—the tendency for some genes to function differently, depending on whether they were inherited maternally or paternally
- --If the gene is maternally imprinted, the allele inherited from the mother is not expressed.
- --If the gene is paternally imprinted, the allele inherited from the father is not expressed.
47
Summary
- Accurate counseling for the family concerning prognosis and recurrence risks depends on correct diagnosis.
- An understanding of the basis of malformation syndromes is important for appropriate management of the patient.
- Accurate counseling for the family concerning prognosis and recurrence risks depends on correct diagnosis.
- An understanding of the basis of malformation syndromes is important for appropriate management of the patient.
Cleft Palate
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