Pedigree Exam Study Guide Flashcards
1
Q
What is a Pedigree?
A
Specialized chart or family tree that uses a particular set of standard symbols
Roman numerals (I, II, III) = generations
Arabric numerals (1, 2, 3) = birth order within generation
EX: Individual identified by both numbers (generation II and sibling 3)
2
Q
What do Roman Numerals Symbolize?
A
(I, II, II) symbolize generations.
3
Q
What do Arabic Numbers Symbolize?
A
(1,2,3) Symbolizes birth order within each generation.
4
Q
What is the objective of a pedigree?
A
The object of a pedigree is to show and analyze the history of inherited traits through generations in a family
5
Q
What is the objective of a pedigree? & what 3 main things do they do.
A
The object of a pedigree is to show and analyze the history of inherited traits through generations in a family
1. Pedigrees provide concise and accurate records of families
2. Pedigrees are helpful in following and diagnosing heritable traits (e.g. diseases and medical conditions), by describing patterns or modes of inheritance
3. Pedigrees are useful in mapping (i.e., locating and isolating) genes that are responsible for certain traits
6
Q
Pedigrees can …..
A
Pedigrees can frequently rule out, but not necessarily prove, a certain mode of inheritance
7
Q
What information must be included on the pedigree? (hint there are 11)
A
PEN AAA PCMDK
1. Proband
2. Race/ethnicity
3. Name First or initials of relatives
-Alternatively, generation-individual numbers (I-1, I-2,
II-1) can be used to maintain confidentiality (HIPAA)
4.Affected status (person with the trait/disease) for each individual in the pedigree
5. Age of all family members, or age at death
- If individual deceased, then cause of death, if known,
is indicated below the person’s symbol
6. Adoption status
7. Pregnancy/abortion
8. Consanguinity (mating within close relatives)
9. Marriage/divorce
10. Date pedigree obtained
11.Key to shading of symbols
8
Q
Human Genome Project primary goals were to:
A
- Discover the complete set of human genes
- Make the information accessible for further biological study
- Determine the complete sequence of DNA bases in the human genome
9
Q
Objective of pedigree:
A
- Show and analyze history of inherit traits through generations (typically used in 3 generations)
– PEDIGREES CAN FREQUENTLY RULE OUT, BUT NOT NECESSARILY PROVE, A CERTAIN MODE OF INHERITANCE
10
Q
Use of Pedigrees?
A
Concise/accurate records of families
Following/diagnosing heritable traits (modes of inheritance)
Mapping - locating and isolating genes for certain traits
11
Q
What is a proband?
A
- Person of interest, the person who is being studied
–IMPORTANT TO DENOTE THE PROBAND IN ORDER TO OBSERVE RELATIONSHIP BETWEEN INDIVIDUALS AND ESTABLISH PATTERNS OF INHERITANCE
– They are noted with an arrow
12
Q
Why is establishing a proband important?
A
IMPORTANT TO DENOTE THE PROBAND IN ORDER TO OBSERVE RELATIONSHIP BETWEEN INDIVIDUALS AND ESTABLISH PATTERNS OF INHERITANCE
13
Q
Monozygotic twins
A
Twins that develop from a single fertilized egg, i.e., identical twins of the same gender
IDENTICAL TWINS
14
Q
Dizygotic twins
A
subsequent fertilization by two different sperms,
i.e. FRATERNAL TWINS fraternal twins of can be same or different genders
15
Q
Homozygous
A
carrying identical alleles for one or more genes
16
Q
Heterozygous:
A
carrying two different alleles for one or more genes
17
Q
Heterogeneity & an example (3)
A
many genes → one phenotype
-Deafness/hearing loss
- Blood clotting disorders
- Blindness
18
Q
Locus:
A
Specific location/place of a gene on a chromosome
Specific location/place of a gene or DNA sequence on a chromosome
Ex: 1q2.4
19
Q
Identify the parts and what is it called?
1q2.4
A
CARB
1= Chromosome
q= Arm
2= Region
4= Band
20
Q
Diploid:
A
Where each chromatid or chromosome unpaired is represented twice in a chromosome paired. One from each parent. Humans are always diploid 46 chromatids/chromosomes unpaired OR 23 Paired chromsomes
21
Q
Haploid
A
One full set of chromatids or Chromosomes unpaired occurring in a mature germ cell OR half the number of chromosomes Paired. 23 chromatids or chromosomes unpaired
22
Q
Ploidy:
A
Number of sets of chromosomes in a biological cell.
23
Q
Aneuploidy:
A
- abnormal number of chromosomes
- EXTRA OR MISSING chromosome
- Occurs during cell division when chromosomes do not separate equally between two daughter cells.
Example/can result in
-Monosomy: deletion of a chromosome (missing 1 chromosome)
- Trisomy: addition of a chromosome (3 chromosomes total). MOST COMMON: 21, 18, 13
- Nullisomy: no chromosome for that pair - lethal
24
Q
Name the three examples of Aneuploidy
A
- Trisomy: addition of a chromosome (3 chromosomes
total). MOST COMMON: 21, 18, 13- . Monosomy: deletion of a chromosome (missing 1
chromosome) - Nullisomy: no chromosome for that pair - lethal
- . Monosomy: deletion of a chromosome (missing 1
25
What is the most common type of Aneuploidy?
Trisomy 21,18 & 13. (somatic cells)
26
Which type of Aneuploidy is lethal?
Nullisomic condition (no chromosome of that chromosome pair is present; 2n -2) - generally a lethal condition
27
Knockout mouse & what is it used for?
genetically engineered mouse with specific genes artificially deleted or inactivated from its genome THE GENES ARE KNOCKED OUT.
- used to study many human diseases (cancer and hearing loss)
28
Knockout mouse:
genetically engineered mouse with specific genes artificially deleted or inactivated from its genome - used to study many human diseases (cancer and hearing loss) THE GENES ARE KNOCKED OUT.
29
Cellular homeostasis:
the tendency of an organism/cell to regulate its internal conditions - maintain health and functioning regardless of external conditions
*they can be affected but only in extremes but otherwise our cells are maintaining homeostasis.
30
Phenocopy & name 2 examples
an environmentally caused trait that mimics a genetically determined trait.
MIMICS A GENETIC CONDITION looks like its happening in the family but really its environmental.
Examples: thalidomide exposure (TE mimics: phenocopy of phocomelia), hair loss from chemotherapy (Chemo mimic: phenocopy of alopecia)
31
Pleiotropy:
one gene or gene pair is going to have a multi system affect on several organ systems and functions resulting in multiple phenotypic effects in the body
Example: Marfan's syndrome
- Autosomal dominant
- Tall, thin, long fingers, heart problems(prone to aneurysm
of the aorta) , dislocated lenses of the eyes, speech
disorders
- Abraham Lincoln
32
Classifications of Genetic Disorders
- Chromosomal abnormalities (number, structure)
- Single gene defect
-Autosomal dominant/recessive
-X-linked dominant/recessive
- Y-linked
- Mitochondrial genetic defect
- Multifactorial /Polygenic Defects
- Environmental influences (spontaneous mutations)
33
Chromosomal abnormalities
(basic)
number & structure
Size (largest to smallest) Chromosome 1= largest. (norm)
Chromosome 22= smallest (norm)
or to chrom y= smallest
Centromere location
34
Single gene defect
(Mandelion Defect)
Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
Y-linked
35
Mitochondrial genetic defect (short)
Bacterial DNA, MT DNA,
36
Multifactorial /Polygenic Defects (Short)
- More than one gene has to be turned on & Also an environmental factor that plays a role. MULTI more then one.
37
Environmental influences (Short)
spontaneous mutations, enviormental affect causes a genetic mutation
- remember now that its been turned on their off springs could/will inherit that genetic mutation
38
Centromere location Types
- Subcentric or submetacentric
P & Q arms are unequal lengths
- Metacentric
Both arms are equal lengths
- Acrocentric
P arm is too short to visualize, but is present
(.13, 14, 15, 21, 22, Y)
- Telocentric (NOT HUMANS)
Centromere located at end of chromosome
- Holocentric (NOT HUMANS)
Entire length of chromosome acts as centromere
39
Subcentric or submetacentric
Subcentric or submetacentric
P & Q arms are unequal lengths
40
Metacentric
- Metacentric
Both arms are equal lengths
41
Acrocentric
- Acrocentric
P arm is too short to visualize, but is present
In humans they are 13, 14, 15, 21, 22, Y
42
Telocentric
- Telocentric (NOT HUMANS)
Centromere located at end of chromosome
43
Holocentric
- Holocentric (NOT HUMANS)- WORMS
Entire length of chromosome acts as centromere
44
CHROMOSOMAL ABNORMALITIES important note
IMPORTANT TO NOTE:
- CHROMOSOMAL ABNORMALITIES HAVE ADVERSE EFFECTS ON MANY SYSTEMS/STRUCTURES IN THE BODY
- MOST PEOPLE WITH UNBALANCED CHROMOSOMES HAVE PRE/POST-NATAL ONSET GROWTH DECIFICENTS AND INTELLECTUAL DISABILITIES
- Infertility or low fertility (downs can reproduce but uncommon)
Exceptions ^^:
Sex chromosomal disorders may have few phenotypic anomalies
Very small deletions/duplications
45
When someone has many malformations, abnormalities in many different structures why would suspect a chromosomal abnormality?
because when you have a chromosomal abnormality in comparison to a gene you will have more Systems affected. because chromosomes have more genes.
typically more then 2 issues
46
Mendelian Monogenic Inheritance:
The inheritance of conditions caused by mutation of a single gene
**just know that it is randomly inherited… and when genes are in close proximity it will always be passed down (not random)** – don't need to know the laws**
47
What are the two things you must have for chromosomal abnormalities?
1. More then 2 systems are affected (multiple malformations & unknown diagnosis)
2. Intellectual disabilities & abnormal growth patterns (pre & post natal ab-normalities)
48
What are the chromosomal abnormality exceptions?
- Sex chromosomal disorders may have few phenotypic anomalies
- Very small deletions/duplications
49
laws of Mendelian Inheritance
Law of Segregation (division)
-Each parent passes a random pair of alleles (gene)
which will separate during cell division.
-Offspring will inherit their own pair of alleles which are
sets of homologous chromosomes from each parent.
- the gene that gets passed is random
Law of Independent Assortment: (goes to offspring)
- Separate genes for separate traits are passed from
parent to offspring INDEPENDENTLY of each other
- ONLY TRUE for genes that are not linked to one another
50
Law of Segregation (division)
The gene that gets passed down is random
-Each parent passes a random pair of alleles (gene)
which will separate during cell division.
-Offspring will inherit their own pair of alleles which are
sets of homologous chromosomes from each parent.
- the gene that gets passed is random
51
Law of Independent Assortment: (goes to offspring)
- Separate genes for separate traits are passed from
parent to offspring INDEPENDENTLY of each other
- ONLY TRUE for genes that are not linked to one another
52
Most cases of genetic deafness recognized today are what...
Most cases of genetic deafness recognized today are
MONOGENIC disorders caused by mutation of a single gene and broadly classified by mode of inheritance
- Autosomal dominant/recessive, x-linked and
mitochondrial
-Syndromic vs non-syndromic
- Proteins coded by genes related to hearing loss are
involved in many functions of the ear
53
What is AD
Autosomal Dominant
54
Mendelian Autosomal Dominant Inheritance:
- One gene in a gene pair is mutated but this change dominates the normal gene and causes an abnormal phenotype
-Affected individuals are heterozygous*
55
Characteristics of AD inheritance
- Vertical transmission
- 50% risk to offspring per pregnancy
- Unaffected individuals cannot transmit the disease
- Males and females equally affected NO GENDER DIFFERENCE
- Variable expressivity and penetrance
-Expressivity: refers to the severity of the genetic
condition apparent for the affected individual
-Penetrance: refers to frequency of occurrence,
usually expressed as a percentage (they have
the gene but do they show it or not)
- AD conditions may appear to skip a generation because the individual carries the gene mutation but does not show it phenotypically
56
what is a vertical transmission?
it occurs and appears in each generation you
57
what is the transmission rate for a autosomal dominate
50% risk to offspring per pregnancy of inheriting the mutant gene
EACH PREGNANCY
58
Expressivity:
refers to the severity of the genetic
EX: in a family you could have the same gene for hearing loss but one sibling is deaf and the other has a mild hearing loss.
59
Penetrance:
refers to frequency of occurrence, usually expressed as a percentage (they have the gene but do they show it or not)
60
what type of inheritance?
Autosomal DOMINATE gene
vertical transmission
61
what type of inheritance?
Autosomal DOMINATE gene
vertical transmission
with incomplete inheritance of #3 & #5
62
what type of inheritance?
Autosomal DOMINATE gene
vertical transmission
63
what type of inheritance?
and
Several of Ben’s family member late-onset SNHL. What is Ben’s risk factor of inheriting the gene?
Autosomal DOMINATE gene
vertical transmission
50% risk factor
64
what type of inheritance?
and
What is the risk of Ben’s son
inheriting the AD gene for hearing
loss?
(late-onset SNHL)
Autosomal DOMINATE gene
vertical transmission
50% if ben has the gene & develops SNHL;
0% if Ben does not
65
what type of inheritance?
Autosomal RECESSIVE
Horizontal Transmission
Parents are Obligate carriers
66
What is Horizontal Transmission?
When a disorder pops up in one genertaion, when there was nothing in the other generations. (recessive)
67
Summary of Characteristics of AD Traits:
-Only one copy of the gene is needed to produce the
phenotype; affected individuals are heterozygotes
-Chance of occurrence per pregnancy is ½ (50%)
- Vertical family pattern
- Persons with the trait have a parent with the trait unless
they represent a spontaneous mutation
- If the line is broken it stays broken
- Incomplete penetrance
- Variable expressivity
- Male : female = 1:1
- Waardenburg syndrome: classic example of variable
expression of the phenotype
68
Characteristics of AR traits
Autosomal Recessive
- TWO IDENTICAL COPIES of the gene are required
- 25% chance of occurrence per pregnancy
- Obligate carrier (heterozygous) parents
- Horizontal family pattern
Family members of the same generation are affected
but not in the other generations
- Males and females are equally affected
- Consanguinity is common
- Founder effect - shared genetic ancestry/limited gene pool resulting in genetic conditions seen far more commonly in certain ethnic groups (we want diversity to filter out the bad genes)
- ALWAYS HOMOZYGOUS
69
what is the transmission rate for a autosomal recessive?
- 25% chance of occurrence per pregnancy of inheriting the mutant gene
EACH PREGNANCY
70
What is AR?
autosomal recessive
71
what type of inheritance?
autosomal recessive
Horizontal tranmission
with Consanguinity
72
Autosomal Recessive Risk Factors
-Consanguinity (same blood/incest) (more likely to get an exact copy of gene
-Obligate carriers (offspring will be a definite carrier - won’t necessarily express)
-Both parents have to be carriers in order for the
offspring to inherit the trait
- They have the genotype but not the phenotype
73
Consanguinity
(mating within the fam)
1st, 2nd & 3rd cousins
Mating connected by double straight lines
74
what type of inheritance?
Autosomal Recessive
Horizontal Tranmission
with carriers
75
what type of inheritance
and who are the obligate carriers?
mom & dad of proband and sibling
76
Risk Calculations for Autosomal Recessive
- Complementary AND non-complementary
- Risk for unaffected sibling to be a carrier
- Pseudo-dominance:
Pseudo dominance is when inheritance of an
autosomal recessive trait mimics an autosomal
dominant pattern; ONE RECESSIVE ALLELE could
cause expression of the trait
- This occurs in the case of x linked recessive inheritance of male offspring
- not homozygous, if two of the same it could balance the bad gene. girl have a supporting X
77
Pseudo-dominance:
Pseudo dominance is when inheritance of an
autosomal recessive trait mimics an autosomal
dominant pattern; ONE RECESSIVE ALLELE could
cause expression of the trait
- This occurs in the case of x linked recessive inheritance of male offspring
- not homozygous, if two of the same it could balance the bad gene. girl have a supporting X
78
Type of inheritance and label obligate carriers
& what is the childs inheritance percentage
- Autosomal recessive
- Non-Complementary Mating
- Vertical transmission BUT it misses first gen so it must
be recessive
- 100% of inheritance of probands children since recessive homozygous
79
Non-Complementary Mating
For Recessive you need TWO IDENTICAL copies of the same gene.
Non-Complementary Mating is when BOTH parents have the exact same identical copy of the gene. resulting in a mutant phenotype. SAME DEAF GENE
80
Complementary Mating
For Recessive you need TWO IDENTICAL copies of the same gene
Complementary mating is when the parents DO NOT have the identical copy of the gene.
they have DIFFERENT DEAF GENE
81
Type of inheritance, label obligate carriers
& what is the childs inheritance percentage
- Autosomal recessive
- Complementary mating for probands parents
- Vertical transmission but when you have two deaf m
produce hearing you know its recessive
- 0% because parents do not have the same deaf gene. and
for recessive you need two identical genes
note you know its not X-linked received because women are showing phenotype in past gens.
82
Type of inheritance and if there are label obligate carriers
X-linked recessive women are carriers who have children with gene. males are showing phenotype because they do not have supporting X
83
Type of inheritance and if there are label obligate
X-linked recessive women are carriers who have children with gene
males are showing phenotype because they do not have supporting X
84
How do you know if its X-linked Dominant or recessive?
- Based on whether or not a female manifests signs of
diseases or is only a carrier
- X-linked recessive is the females are carriers, not
expressing
- X-linked dominant, females manifest some signs of the
disorder
- Affected males can only have carrier daughters for
recessive
- Affected males will transmit the trait to daughters if
dominant
85
X-Linked Inheritance
- Commonly divided into X-linked recessive and X-linked
dominant
- Based on whether or not a female manifests signs of
diseases or is only a carrier
- X-linked recessive is the females are carriers, not
expressing
- X-linked dominant, females manifest some signs of the
disorder
- Affected males can only have carrier daughters for
recessive
- Affected males will transmit the trait to daughters if
dominant
- No male to male transmission (son will only take the Y
from dad, leaving the X)
- Males are affected worse because they don't have the balancing X
- Traits controlled by genes on the X chromosome are defined as dominant or recessive by the phenotype of the females - hemizygous (one X)
86
hemizygous
is 1/2
men are hemizygous for all genes on the X chromosome because they are neither heterozygous nor homozygous for the X chromosome
Different chromosomes (XY)
ONLY FOR MALES
87
Pseudo-dominance:
- Pseudo-dominance:
Pseudo dominance is when inheritance of an
autosomal recessive trait mimics an autosomal
dominant pattern; ONE RECESSIVE ALLELE could
cause expression of the trait
- This occurs in the case of x linked recessive
inheritance of male offspring
because they do not have the balancing X.
88
X-Linked Recessive Characteristics
- Only need one bad gene for (men to show)
- No father to son transmission
- The mutant gene is on the X chromosome
-Transmission from unaffected female carriers to males
- All daughters of a male with the trait will be carriers
- Carrier females will have a
- 50% chance to have sons with abnormal trait
-50% to have carrier daughters
- 50% to have normal offsprings
- The abnormal trait may be transmitted through a series of carrier females
89
For X-Linked recessive Carrier females will have a inheritance percentage of what?
- Carrier females will have a
- 50% chance to have sons with abnormal trait
-50% to have carrier daughters
- 50% to have normal offsprings
90
Name the inheritance type and the obligate carriers
X-Linked Recessive
91
Examples of X-linked Inheritance
Color blindness
Hemophilia
X-linked hearing loss with stapes gusher
Muscular dystrophy (Duchenne - type)
92
what is the inheritance percentage for X-Linked Dominate
If dad is affected
sons have 0% chance since they receive Y
daughters have a 50% chance
If mom is affected
BOTH SONS AND DAUGHTERS HAVE A 50% CHANCE OF INHERITING THAT TRAIT FROM THEIR MOTHER AND EXPRESSING
93
X-linked Dominant Inheritance Examples
Alport’s Syndrome
- Collagen gene mutation
- Affects BM of cochlea and kidneys
- May also affect eyes
94
Y-Linked Inheritance
Rare! Passed from father to son (the fathers Y has to be passed down to be the sons Y)
No father to daughter transmission
Many of these Y transmitted mutant traits are involved in abnormal male sexual development
