double cross over phenotypes

low probability of occurrence, must be present in the last numbers

*Klinefelter Syndrome (XXY)

underdeveloped sex organs, breast development, large hands, and long arms and legs, low sperm count (infertile )

-wide hips (most unaware)

-caused by nondisjunction

-1 in 660 males

*Turner's Syndrome (Monosomy X)

-only an X chromosome

-females (no Y)

-nonfunctional ovaries (infertile)

-short in stature

-caused by nondisjuction

-1 in 2000 births

*Nondisjuction

the failure of one or more pairs of homologous chromosomes or sister chromatids to separate normally during nuclear division, usually resulting in an abnormal distribution of chromosomes in the daughter nuclei.

-during anaphase of meiosis I or meiosis II

babies with only a (Y chromosome and no X)..

Do not survive

*TDF

testis determining factor

-functions as transcription factor

-master switch

*mosaic genetics

the presence of two or more populations of cells with different genotypes in one individual who has developed from a single fertilized egg

*Barr body

Inactivated X chromosome (N-1)

-XXXY = N-1→3-1= 2 barr bodies

XIST

X-inactivation specific transcript gene. only gene known to be transcribed only from inactive X chromosome

autosomes

Any chromosome that is not a sex chromosome

*3X:2A

metafemale

*2X:2A (1.0)

female

*3X:4A

intersex

*X:2A (0.5)

male

*XY:2A (0.5)

male

*XY:3A

metamale

*2 sets of autosomes + X Y

male (XY: 2A (autosomes, 1 or X and 1 for Y equals 2 autosomes or A)

-factors that cause a fly to developed into a male are NOT located on the sex chromosomes but are instead found on the autosomes.

*C. Elegans

consists of males and hermaphrodites (Testes and ovaries)

-the majority of offspring are hermaphrodites only 1% are males male x hermaphrodites = half male(X), half hermaphrodite (XX) offspring

-Lack Y chromosomes altogether, depending on the expression of the X chromosome and autosomes

*TSD

temperature-dependent sex determination

aromatase

enzyme that converts testosterone to estradiol or estrogen (TSD)

*aneuoploidy

one chromosome extra or less but not a complete set-better tolerated in the plant kingdom-Most chromosome abnormalities are aneuoploidy

*monosomy

missing a chromosome (2n-1)

-embryos more likely to die, therefore trisomy more common in births. A shortage of chromosome considered more lethal

*polyploidy

condition in which an organism has extra sets of chromosomes

-more common in plants, fish, lizards, amphibians

*euploidy

the correct number of chromosomes in a species

*Haploinsufficiency

The phenomenon occurs when a person has only a single functional copy of a gene, and that single functional copy does not produce a normal phenotype. Shows a dominant pattern of inheritance.

-insufficient to provide life

-sustaining function for the organism

*Trisomy

-3 copies of a chromosome

-produces more viable offspring than monosomy in plants and animals species

larger chromosomes cause..

greater genetic imbalance than smaller chromosomes

*trisomy 21 (Down Syndrome) (47, 21 +)

A human genetic disorder resulting from the presence of an extra chromosome 21; characterized by heart and respiratory defects and varying degrees of mental retardation. 1-800 births (50 yr avg)

-20x more chance of leukemia

-Alzheimer's disease

-DSCR

-Ovum is a source mainly

CVS

chorionic villus sampling

*Autopolyploidy

an individual that has more than two chromosome sets that are all derived from a single species

-increase in size of organism due to larger cell size not # of cells

*Allopolyploidy

Extra sets of chromosomes come from different species, arise from hybridization, new chromosomes have no homologs, can create new species if followed by autopolyploidy

-need balance of genes, so tetraploids (4n) are more likely to be found in nature as an unbalance in games result in an odd number of chromosomes

G1 cyclins

Proteins are present in most but not all cells, they form complexes with Cdks and help to regulate the activities of G1/S cyclins

-suppressed when ploidy increases. stays in G1 phase due to not moving through cycle b/c of suppressed Cyclins, therefore growing larger before moving beyond the G1 phase (Auto- polyploidy)

*amphidiploid (cotton)

allotetraploid where both original species are known

-Cultivated American cotton "Gossypium"

-treated with colchicine to double chromosome #, resulted in fertile amphidiploid variety of cotton, 26 pairs of chromosomes, and similar characteristics similar to cultivate variety

Triticale

hybrid of wheat and rye

-increases grain production, good qualities of both species combined into hybrid

*translocations of chromosomes

when a chromosome breaks off a part of itself and transfer it to another chromosome

-aberrations often lead to gametes that are duplicated or deficient in chromosomal regions

*terminal deletions

when the deletion involves the p or q end

*intercalary deletion

deletion from the interior of the chromosome

*compensation loop

Synapsis between chromosome with large intercalary deletion and normal complete homolog

-Requires unpaired region of normal homolog to loop out of linear structure into deletion or compensation loop

*Cri Du chat Syndrome (46, 5- )

A deletion of the short arm of chromosome 5 is associated with an array of congenital malformations, the most characteristic of which is an infant cry that resembles a meowing cat.

-intellectual disability, small head, delayed development, abnormalities in the glottis and larynx leading to the cat-like crying sound

-considered a terminal deletion

-partial monosomy but best considered a segmental deletion(some or all of the p arm or short arm is missing on chromosome 5)-1 in 20k-50k births, not usually inherited

-deletion in the Telomerase reverse transcriptase (TERT) has been implicated in various phenotypic changes

*duplications

chromosome segment is repeated on same chromosome

-result of unequal crossing over

-essential to the origin of new species during evolution

-New function may impart an "adaptive" advantage to organisms (over long evolutionary periods before)

-genes with duplication acquire many mutations, while sustaining its essential function.

-short period of time, the duplicated gene or the new genetic information may have no particular advantage

ex.) hemoglobin and myoglobins (DNa sequences in common, but whose gene product are distinct)

*deletions

losses of nucleotide pairs in a gene

-caused by breakages or losses in chromosomes in some places

*gene redundancy

the phenomenon in which another gene with a similar function compensates for an inactive gene

Bar-Eyed flies

narrow, slit-like eyes

-dominant X linked mutation

-caused by duplication of genes on chromosomes

*Copy number Variation (CNV)

differences among individuals in the number of copies of a region of the genome.

-Sometimes larger or smaller number of copies

-found in coding and non-coding regions of the genome

-5-10% of the human genome-cardiovasular disease, cancer, autism, and Type I diabetes

-greater reduction of the gene DEFB, greater chance of Crohn's disease (affects colon)

*inversions

When a fragment of the chromosome is reversed

-doesn't involve lose of genetic info, but simply rearranges the linear genetic sequence

-requires two breaks along the length of the chromosome

-"sticky ends" brought close together and rejoined

*paracentric inversion

inversion that does not include the centromere

*pericentric inversion

inversion that includes the centromere

*inversion loop

a loop formed by meiotic pairing of homologs in an inversion heterozygote

-could result in inversion heterozygote

crossing over doesn't occur within the inverted segment of the inversion loop..

the homologs will segregate, results in two normal and two inverted chromatids

crossing over does occur within the inversion loop..

abnormal chromatids are produced

*dicentric chromatid

chromatid with two centromeres

-during anaphase, the dicentric chromatid is pulled into two directions

-usually breaks at some point, so that part of the chromatid goes into one gamete and part into another gamete during meiotics divisions

*acentric chromatid

lacking a centromere

-during anaphase, randomly moves to one pole or the other or may be lost

*single cross over (SCO)

Exchange of genetic material between homologous chromosomes at a single locus

-occurs between two non-sister chromatids NOT between the two loci

-therefore the cross

-over is not detected because no recombinant gametes are produced

-other two chromatids of the tetrad are not involved in the exchange and enter the gamete unchanged

*dicentric and acentric chromatids

are defficent in genetic material,

-In fertillization, the zygote most often develope abnormally, if at all

*inversion...

suppresses crossing over

-due to offspring bearing crossover gametes are inviable and not recovered, possibly due to the suppression of crossing over

-inversion perpetuated within the species, therefore the cycle is repeated continuously during meiosis in future generations

-phenomenon due to crossover chromatids ending up being abnormal in genetic content

-due to the recovery of crossover products it is suppressed in inversion heterozygotes, groups of specific alleles at adjacent loci within inversion may be preserved from generation to generation

-Ghengas Kahn lineage? (Ask professor)

balancer chromosomes

a chromosome containing one or more inversions that suppress crossing over with its homolog and which carries a dominant marker that is usually lethal when homozygous

-organism is heterozygous for a balancer chromosome, desired sequences of alleles are preserved during experimental work

*Reciporcal translocation

results from the exchange of chromosome segment between 2 nonhomologous chromosomes & there is no gain or loss of genetic info

-rearrangement of genetic material

-doesn't directly alter the viability of individuals bearing it

Homologs that are heterozygous for a reciprocal translocation undergo

unorthodox synapsis during meiosis

-pairing results in cross-like configuration

-genetically unbalanced gametes produced due to the unusual alignment during meiosis

*aberrant gametes..

are not necessarily the result of crossing over due the law of independent assortment, as the chromosome containing centromere 1 travels with either chromosomes of different centromeres

*alternate segregation

A pattern of chromosome segregation that can occur following reciprocal balanced translocation that leads to the production of viable gametes.

*adjacent segregation

Leads to gametes containing duplications and deficiencies

-if participates in fertilization, lethality often occurs

-results in semisterility, plays role in evolution

-in humans results in monosomy and trisomy

*Robertsonian translocation

Translocation in which the long arms of two acrocentric chromosomes become joined to a common centromere, resulting in a chromosome with two long arms and usually another chromosome with two short arms.

-accounts for cases of familial down syndrome which is inherited

-occurs much higher frequency over several generations "runs in families"

familial down syndrome

a parent has 14/21, D/G translocation, individual is phentotypically normal, even though they only have 45 chromosomes (carrier is unaffected)

-small region is lost from both chromosome 14 and 21 during a translocation event

-another case, parent could have 46 chromosomes, 1/4 of the time, also exhibit down syndrome

*gametes unbalanced upon fertilization = lethality occurs

*fragile sites

Areas on chromosomes that develop distinctive breaks or gaps when cells are cultured in the absence of folic acid which is normally present in medium cultures

-regions of chromosomes that are not 'tightly coiled'

-may result in intellectual disabllity and cancer

-most fragile sites do not appear to be associated with any clinical syndrome

* Fragile X Syndrome (FXS)

most commonly inherited cause of intellectual disability and occurs when a DNA series makes too many copies of itself and turns off a gene on the X chromosome

="gap region" associated with FXS, shown in picture where the arrow is pointing←

-Gene responsible is FMR1 (CGG) caused by trinucleotide repeats, also recognized in Huntington's disease and myotonic dystrophy

-in "upstream region" area adjacent to coding sequence of the gene

-individuals bearing a folate-sensitive site on the X-chromosome

-1-4000 males (all males bearing this X chromosome have it due to only have one X chromosome)

-1-8000 females (60% of females have it, due to having two X chromosomes)

-characteristics include:

→long, narrow faces

→protruding chins

→enlarged ears

-Normal human: 6 and 54 repeats

-carriers: 55 to 230 repeats

*230 + repeats = Fragile X Syndrome (FXS)

-FMR1 normal product = RNA-binding protein, FMRP known to be produced in the brain

-Absence of this protein due to inactivation caused by methylation results in intellectual disability

-linked to cancer from fragile site FRA3B on 'p' arm of chromosome 3 is often altered or missing

-FHIT - located on fragile sites, increase chance to mutations and deletions

*gene anticipation

Number of CGG repeats continues to increase in future generations

-230+ repeats exceeded, retardation becomes more severe in each successive generation as the repeats increase

-Occurs by maternal parent (mother) not the father the repeats over 230+

trivalents

pairing of 3 chromosomes

*Lyon hypothesis

the proposal that dosage compensation in mammalian females is accomplished by partially and randomly inactivating one of the two X chromosomes

*linkage

occurs when different traits are inherited together more often than they would have been by chance along; it is assumed that these traits are linked on the same chromosome

-chromosomes are the are the unit of transmission not the gene during meiosis

-*linked genes are not free to undergo independent assortment

-instead transmitted as a unit

*recombination

the genetic process by which one chromosome breaks off and attaches to another chromosome during reproductive cell division

-occurs during tetrad stage

*complete linkage

linkage between genes that are located close together on the same chromosome with no crossing over between them

-exchange creates recombinant or crossover gametes

-seldom occurs between two genes

-results in all parental gamates offspring

-# of progeny is usually small

*The frequency at which crossing over occurs between two linked genes depends on _____.

the distance separating the respective loci along the chromosome

-*The closer two genes are, the less likely there is to have chiasma form between them, therefore less genetic exchange between two genes close together

-Morgan first to propose 'crossing over' to describe physical exchange leading to recombination

*As the distance between two genes increases...

the proportion of recombinant gametes increases and that of parental gametes decreases

-does not exceed 50%

-if 50 percent recombination occurs, the result is 1:1:1:1 (two parental, two recombinant gametes)

-*when genes are really close together, during meiosis or crossing over, they move as one gene, not two separate genes; However, if the genes are further apart, they are treated as two separate genes therefore increasing the likelihood of recombination because both genes are being crossed over as a separate entity and not treated as one gene.

-*expressed usually in F2 generation

*linkage ratio

-Complete linkage between two genes due to close proximity

-Unique F2 phenotypic ratio results

*linkage groups

groups of traits that tend to appear together because they are on the same chromosome.

-# of linkage groups should correspond to the haploid number of chromosomes

*chiasmata

X-shaped regions where crossing over occurred.

-Morgan proposed that Chiasmata could represent points of genetic exchange

-Morgan postulated that if an exchange occurs during gametic formation between mutant genes on the two X chromosomes of the F1 females, the unique phenotypes would occur

-linked genes exist in *linear order

*chromosome mapping

process for determining the relative position of genes on a chromosome

-each number represents the percentage of recombinant offspring produced

crossing over in Drosophila only occurs in...

female Drosophila

-occurs in both sexes in most organisms

-made genetic mapping less complex

-discovered by Sturtevant

*The chromosomal theory of inheritance states that

chromosomes are carriers of genetic information and occur in linear order equivalent of Mendel's unit factors

*The closer two loci reside along the axis of the chromosome...

the less likely any single

-cross over (SCO) event will occur between them

*The farther apart two linked loci are...

the more likely a random crossover event will occur between them

-a cross over occurs, yielding gametes

*The percentage of tetrads involved in an exchange between two genes is...

TWICE the percentage of recombinant gametes produced

-Therefore, Theoretical limit of observed recombination due to crossing over is *50%

More than 50 m/u or more than 50% between two linked genes

a cross over expected to occur 100% of the tetrads

-rarely if ever happens the ratio would have to be 1:1:1:1

*double cross over

Exchange of genetic material between homologous chromosomes at two loci

-usually three gene pairs, each heterozygous for two alleles

-requires large # of offspring to detect a DCO when closely linked genes are involved

*DCO undetected because no rearrangments of alleles occurs

*non-cross over phenotypes

most easily recognized because they 'exist in the greatest proportion'

*As the distance between Two genes increases...

mapping estimates become more inaccurate

-mapping determinations usually underestimate the actual distance between two genes

*The further apart two genes are, the greater the probability that undetected cross overs will occur

-more accurate maps from experiments where genes are relatively close together

*Interference in genetic mapping

phenomenon through which a crossover event in one region of the chromosome inhibits a second event in nearby regions that causes this reduction

*The closer genes are to one another along the chromosome.. (in terms of inference in genetic mapping)

The more positive interference occurs

interference decreases as the genes are located further apart

DNA markers

Sequence variations among individuals in a specific region of DNA that are detected by molecular analysis of the DNA and can be used in genetic analysis.

-Cystic fibrosis (exocrine disorder)

SNPs (single-nucleotide polymorphisms)

variations in the DNA sequence that occur when a single nucleotide in the genome is altered

*sequence maps

give an exact order of bases in a plasmid, chromosome, or entire genome

SCEs (sister chromatid exchanges)

Reciprocal exchanges similar to crossing over

-Between sister chromatids (crossing over is between NONsisters)

-DO NOT produce new allelic combinations

-X-Rays, UV light, certain chemical mutagens) increase the frequency of SCE's

harlequin chromosomes

sister chromatids involved in mitotic exchanges-patch

-like appearance when stained and viewed under a microscope

Bloom Syndrome

The frequency of SCEs is elevated in Bloom Syndrome, caused by mutation in the BLM gene on chromosome 15.

-recessively inherited

-benign tumors, abnormal behavior patterns

-increased breaks rearrangements between nonhomologous chromosomes in addition to excessive SCEs

-BLM gene encodes for enzyme called 'DNA Helicase", which is best known for its role in DNA replication