patterns of inheritance Flashcards
pedigree
chart/family tree that uses sets of symbols
-objective is to show the history of inherited traits through generations
-frequently rule out a certain mode of inheritance but not prove
how to show generations in a pedigree
marked vertically by roman numerals
-I being generation 1
how to show birth order on a pedigreee
marked horizontally by number 1, 2, 3 ….
-done individually with each generation
-typically oldest to youngest as you move to the right
-connected through horizontal lines above the symbols
how to show multiple siblings in one symbol
have that gender shape with the number there is present in the family
proband
who it is about, consultant
-marked by : an arrow on the bottom of the symbol pointing towards the shape
what must be included in a pedigree
proband, race/ethnicity, first name/initial of relatives, affected status for each individual, age of family members (or age of death), adoption status, pregnancy/abortion, consanguinity, marriage/divorce, mating, carrier status and is they are twins
how to show what the shading is of each individual
use a key with symbols to show what the shading means
-if multipole disorders are present, can use multiple shading/patterns
monozygotic twins
identical
-develops from a single fertilized egg and therefore must be the same gender
-splitting of zygote at any stage
-both implant separately
-more rare
dizygotic twins
fraternal
-develops from 2 eggs being fertilized by two different sperms
-they are no more similar than two siblings
carrier
you have the gene, but do not show the phenotype
-only occurs in recessive traits
locus (loci)
specific location of a gene or DNA sequence on a chromosome
-chromosome number, arm, region and band
-the numbers go outward from the centromere (meaning 1 is closest to the centromere and increases as you go outward)
homozygous
carrying identical alleles for one or more genes
-same allele, same gene
heterozygous
carrying two different alleles for one or more genes
-1 bad, 1 good
heterogeneity
variation within genes and phenotypes
-many genes can lead to the same phenotype
-for example HL/deafness has tons of genes that can result in it
ploidy
number
diploid cell
double number of chromosomes found in a mature germ cell
-somatic has 46 (23 pairs)
germ cells
egg and sperm cells
-haploid with half the number of chromosomes (23)
aneuploidy
abnormal number of chromosomes, can be extra or missing
-occurs at cell division and the cells do not separate equally between daughter cells
-leads to chromosomal abnormalities
knockout mouse
genetically engineered mouse with specific genes artificially deleted
cellular homeostasis
tendency of a cell or organisms to regulate its internal conditions, such as chemical composition of body fluids, to maintain health and functioning regardless of external conditions
phenocopy
environmentally caused trait that mimics a genetically determined traits
-it is not inherited but makes the conditions look as if they were
-ex. hair loss from chemotherapy can mimic the phenotype of alopecia
pleiotrophy
diverse effects of one gene or gene pair on several organ systems and functions resulting in multiple phenotypic effects in the body
-all syndromic due to affecting multiple organs
-example is marfan’s syndrome which is a genetic disorder of connective tissue (that develops into a lot of things within the body)
how do we classify genetic disorders
by chromosomal abnormalities, by single gene defect, by mitochondrial defect, by multifactorial/polygenic defect and by environmental influences
chromosomal abnormalities
will have effects on many parts of the body and most people with unbalanced chromosomes have pre- or post-natal onset growth deficiencies and intellectual disability (for example stunted growth)
-an individual with 2 anomalies is unlikely to have this with exception of sex chromosomes due to them being small
subcentric or submetacentric
p and q arms are unequal lengths
metacentric
two arms are roughly the same length
acrocentric
p arm is so short it is hard to observe
-in humans 13, 14, 15, 21, 22 and Y are this type naturally
telocentric
the centromere is located at the terminal end of the chromosomes
-not present within humans
holocentric
entire lengthe of the chromosome acts as the centromere
-found within worms and not within humans
mendelian or monogenic inheritance
inheritance of conditions is caused by mutation of a single gene
-has 2 laws (segregation and independent assortment)
-most causes are caused by a single gene and are classified by a mode of inheritance
1st law
law of segregation
-each parent passes a randomly selected gene copy or allele to the offspring
-the offspring will receive a pair of alleles of that gene for the trait by inheriting sets of homologous chromosomes from the parents
2nd law
law of independent assortment
-separate genes for separate traits are passed from parents to offspring independently of one another
-biological selection of one gene has nothing to do with the selection of the other gene
what are the single gene defects
autosomal dominant, autosomal recessive, x-linked dominant, x-linked recessive , y-linked
autosomal dominant (AD)
you only need one bad gene to show the phenotype
-the bad gene “overpowers” the good gene to cause an abnormal phenotype
-mom or dad can pass it down
-affected people are heterozygous
characteristics of AD
-vertical transmission (each generation will have it)
-unaffected individuals cannot transmit the disease
-males and females are affected equally
-variable expressivity and penetrance
expressivity
the severity of the genetic condition for the affected individuals
-how it expressed
penetrance
frequency of occurrence
-some can manifest later in life
-some could appear to have skipped a generation because they show no sign or symptoms
what are the risks of the child within AD
50% per pregnancy since only one copy is needed
-can be DD, Dd or dd (anything with D will have it)
autosomal recessive
two identical copies of the bad gene are needed to show the phenotype
-family members of the same generation are affected but not in other generations
-parents are carrier’s
characteristics of AR
-two copies are needed
-will result in a homozygous offspring
-carrier parent is required
-horizontal family pattern
-either male or female can transmit the trait
-equal chance in both males and females
what are the risks of the child within AR
50% chance a carrier, 25% they have it, 25% chance they do not have it per pregnancy
-can be RR (will have it), Rr (carrier), rr (has it)
complementary mating
different genes but same phenotype
-when they mate offspring is not affected
-for example 2 deaf parents with different genes when mate will have an offspring that is not affected
non-complementary mating
same gene and same phenotype
-parents are carriers and the offspring will be affected
pseudo dominance
one recessive gene could result in the expression of the phenotype
-inheritance of a recessive trait mimics and autosomal dominant pattern
x-linked recessive
females are carriers with no signs of the disease and males will show the phenotype when affected
-since men are hemizygous, they just need a gene error on the X to cause the disease (XY)
-women have two X genes so they are homozygous so need both bad genes
characteristics of x-linked recessive
-no father to son transmission
-transmission from unaffected female carriers to males is a 50% chance (can give the good or bad)
-all daughters of a male with the trait will become carriers (since they have to pass down the X)
-trait may be transmitted through a series of carrier females (meaning multiple generations of carriers before a phenotype)
what are the risks of the child within x-linked recessive
-50% unaffected and 50% carrier for females
-50% unaffected and 50% affected for males
x-linked dominant
females with the abnormal gene on one X chromosome will manifest the disease condition regardless of what is on the other X chromosome
-all you need is 1 bad gene
characteristics of x-linked dominant
-females if affected will show sings, if males are affected will show signs
-no father to son transmission
what are the risks of the child within x-linked dominant
-both sons and daughters have a 50% chance of inheriting the condition from the mother
-the son will not be affected and the daughter has a 100% chance of being affected if inherited from the father
how to differentiate x-linked recessive from x-linked dominant
look at the male offspring of the father
-the son should be unaffected because he will inherit the Y from his father BUT the daughter will show the disorder if affected with dominant
y-linked
expressed only to male offspring because the father has to pass the Y to the son
-traits encoded on the y are passed directly from father to son
-there is no balancing of the mutant Y gene by X or another Y
-no transmission from daughter from father
-many Y traits are involved in abnormal male sexual development which results in decreased fertility
multifactorial
traits result from the interplay of multiple environmental factors with multiple genes
-commonly associated with sporadic gene mutations
-example is oculo-auriculo-vertebral (OAV) spectrum disorder
polygenic
traits or diseases caused by the impact of many different genes
-each gene has a small individual impact on the phenotype
-these traits are quantitative meaning the more genes involved, the more severe the manifestation will be
-example is cleft lip/palate
mitochondrial inheritance
vertical pattern from mom, all generations will be affected
-during meiosis, the mitochondria are passed from the mother to the occyte (sperms do not contribute cytoplasm during fertilization which is where mitochondria is located)
-no children of fathers with the trait will inherit it
-ALL children of an affected mother will be affected
genomic imprinting
process in which the phenotype differs depending upon which parent transmits a particular allele or chromosome
-phenotype will vary based on if it’s from mom or dad
-it is the same gene mutation but will result in a different phenotype
-example deletion of chromosome 15 will result in prader willi syndrome (paternal origin) and angelman syndrome (maternal)
anticipation
due to allelic expansion, severity will get worse
-worsening of symptoms of a genetic disease from one generation to the next
allelic expansion
the increase in gene size that occurs from the number of trinucleotide base sequences increasing
what are examples of allelic expansion and anticipation
huntington’s disease (AD pattern)
-gene on tip of chromosome 4p
-normal has 6-37 but in an affected there is 35-121 copies
why are men hemizygous? why are female homozygous?
men have XY, two different chromosomes
females have XX, two same chromosomes
what chromosomes are most common with trisomy?
13, 18 and 21 within somatic cells
what are the differences between autosomal dominant and autosomal recessive?
dominant : only need one bad gene to show the phenotype, if someone gets it they show it
recessive : need two identical to show the phenotype, includes carriers
what are the differences between x-linked dominant and x-linked recessive
dominant : in females one will show the phenotype and in males one will show the phenotype, if inherited from the father from the daughter they will be affected
recessive : in females need two bad genes and in males only one will show the phenotype, if inherited from the father in a daughter they will be a carrier
why are y-linked patterns rare?
the y chromosome is the smallest chromosome with a small amount of genes
if you see carriers on a pedigree, what does this indicate right away?
it is a recessive type of inheritance
what is an important characteristic about chromosomal abnormalities?
they affect multiple systems
what are two common characteristics of chromosomal abnormalities?
growth defect and intellectual disability
monosomic
only one copy of the chromosome is present
-missing one
trisomic
extra copy of a chromosome
-added one
nullisomic
no chromosome of that pair is present
-not survivable
multifactorial vs. polygenic
multifactorial : multiple genes with the environment
polygenic : multiple genes interplaying together
example of AD inheritance
waardenburg syndrome
example of AR inheritance
sickle cell anemia
example of x-linked recessive inheritance
colorblindness or hemophilia
example of x-linked dominant inheritance
alport’s syndrome
example of y-linked inheritance
webbed toes
example of mitochondrial inheritance
leber’s hereditary optic neuropathy
